Original Article
Clinical Responses to Undiluted and Diluted Smallpox Vaccine
N Engl J Med 2002; 346:1265-1274April 25, 2002
- Abstract
Background
To evaluate the potential to increase the supply of smallpox vaccine (vaccinia virus), we compared the response to vaccination with 108.1, 107.2, and 107.0 plaque-forming units (pfu) of vaccinia virus per milliliter.
Methods
In this randomized, single-blind, prospective study, 680 adults who had not been previously immunized were inoculated intradermally with undiluted vaccine (mean titer, 108.1 pfu per milliliter), a 1:5 dilution, or a 1:10 dilution of vaccinia virus with use of a bifurcated needle, and the site was covered with a semipermeable dressing. Subjects were monitored for vesicle formation (an indicator of the success of vaccination) and adverse events for 56 days after immunization.
Results
Success rates did not differ significantly among the groups and ranged from 97.1 to 99.1 percent after the first vaccination. Both the undiluted and diluted vaccines were reactogenic. In addition to the formation of pustules, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills consistent with the presence of an acute viral illness. Generalized and localized rashes, including two cases of erythema multiforme, were also observed.
Conclusions
When given by a bifurcated needle, vaccinia virus vaccine can be diluted to a titer as low as 107.0 pfu per milliliter (approximately 10,000 pfu per dose) and induce local viral replication and vesicle formation in more than 97 percent of persons.
Media in This Article
Figure 1
Semipermeable Adhesive Dressing.Figure 2
Photographs of Primary Reactions and Common Adverse Events after Vaccination with Vaccinia Virus.Article Activity
- Article
Developing public health strategies to counter bioterrorism threats from smallpox is a high national priority.1 In the event of an emergency, there is an insufficient supply of smallpox vaccine (vaccinia virus) available to vaccinate all U.S. residents with the recommended quantity of virus. Thus, it is important to determine whether current stocks could be diluted, administered with a traditional bifurcated needle, and still result in a high incidence of viral replication in the skin with vesicle formation.
On the basis of the results of a pilot dose-ranging study reported elsewhere in this issue of the Journal, 2 we sought to determine with greater precision (within 5 percent) the rate of success of inoculation with dilutions expected to have a moderate-to-high success rate: undiluted vaccine (geometric mean titer, 108.1 plaque-forming units [pfu] per milliliter), a dilution of 1:5 (geometric mean titer, 107.2 pfu per milliliter), and a dilution of 1:10 (geometric mean titer, 107.0 pfu per milliliter). Given the reactogenicity consequent to viral replication in previously unexposed persons, we also sought to determine the frequency and range of adverse events associated with the administration of the vaccine with a bifurcated needle at these dilutions.
Methods
Vaccine and Diluent
The smallpox vaccine (Dryvax, Wyeth Laboratories, Marietta, Pa.) used in this study was produced in 1982 or earlier (lot no. 4008284) and was provided by the Centers for Disease Control and Prevention in Atlanta. The vaccine lot and diluent differed from the preparations used in the pilot study, and the vaccine contained a larger quantity of virus (108.1 vs. 107.8 pfu per milliliter).2 Lyophilized vaccine was reconstituted with a new formulation of diluent (lot no. 1468-1A, Chesapeake Biological Laboratories, Baltimore) consisting of 50 percent glycerin and 0.21 percent phenol in sterile water. Unlike the original vaccine diluent, this formulation did not contain brilliant green dye.
The vaccine was prepared at each site by adding 0.25 ml, 1.25 ml, or 2.5 ml of diluent directly to the vials, which corresponded to undiluted vaccine, a 1:5 dilution, and a 1:10 dilution, respectively. Vaccine was used for up to seven days after reconstitution and stored at 2 to 8°C between uses in accordance with the results of analyses of the stability of vaccinia virus. An aliquot from each dilution of vaccine used at each site was collected at the time of preparation and frozen for subsequent evaluations of the viral titer. Titers of every vaccine preparation were determined by plaque assay in the central laboratory (Saint Louis University, St. Louis).3 The quantity of virus on three representative bifurcated needles was also measured by plaque assay.
Study Design and Subjects
The study was a randomized, single-blind trial conducted at the National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation units in St. Louis, Baltimore, and Rochester, N.Y., and at the Respiratory Pathogens Research Unit in Houston. The study was approved by the institutional review board of each participating facility. Subjects were enrolled from November 2 to November 28, 2001, after providing written informed consent.
Healthy adults 18 to 32 years of age were eligible if they had no vaccination scar, no history of vaccinia virus vaccination, and no antibodies against human immunodeficiency virus. In the wake of the September 11, 2001, terrorist attacks, public announcement of the study resulted in a vigorous public response among young adult volunteers. Many were students at the participating trial sites. Exclusion criteria included the contraindications against vaccination noted in the package insert (pregnancy, immunosuppression, and eczema), a history of vaccination with any type of live attenuated virus within 60 days before the study, the receipt of blood products or immune globulin within 6 months before the study, and household contact, sexual contact, or occupational exposure to pregnant women, immunosuppressed persons, persons with eczema, or infants less than 12 months of age.
A total of 680 subjects were randomly assigned to receive undiluted vaccine, a 1:5 dilution of vaccine, or a 1:10 dilution of vaccine. The subjects were inoculated with a bifurcated needle that held a drop of vaccine and that was pressed 15 times into the skin of the upper arm. The vaccination sites were covered with folded gauze and a semipermeable adhesive membrane to avoid autoinoculation or exposure of personal contacts to vaccinia virus (Figure 1Figure 1
Semipermeable Adhesive Dressing.).2 Dressings were changed and the vaccination sites were assessed every three to five days until the lesions dried and an eschar formed. Subjects were evaluated for adverse events for 56 days after immunization.The primary end point was the rate of success of vaccination. Success was defined by the presence of a primary vesicle at the inoculation site seven to nine days after scarification, as described previously.4 To increase the rate of success of vaccination, subjects who had no evidence of vesicle formation by days 7 through 9 were revaccinated between days 7 and 17 with the same dilution of vaccinia virus.
Neutralizing Antibody and Vaccine-Stability Assays
Serum samples were collected before vaccination (day 0) from all subjects. Serum neutralizing antibody titers were determined in prevaccination samples from all 15 subjects in whom the initial vaccination failed, as well as in 28 subjects in whom vaccination was successful. The end point was a 60 percent reduction in the number of plaque-forming units, as described previously.3 In addition, plaque assay was used to determine the stability of the vaccine reconstituted with the new diluent after storage at 2 to 8°C.5
Statistical Analysis
The goal of the study was to establish precise estimates of the rates of response to a 1:5 dilution and a 1:10 dilution and secondarily to test the hypothesis of the noninferiority of these dilutions as compared with undiluted vaccine. Noninferiority was defined by an alpha level of 0.05 and a difference in success rates (the rate for undiluted vaccine minus the rate for diluted vaccine) of no more than 5 percent. The sample size was based on the results of the pilot study.2 We estimated that 684 subjects would need to be enrolled — 107 in the group given undiluted vaccine, 241 in the group given a 1:5 dilution, and 336 in the group given a 1:10 dilution. We used exact methods to calculate the 95 percent confidence intervals for the success rates in each group and for the differences in these rates among the groups.6 We used a one-sided t-test to calculate the confidence intervals for the difference in rates, in keeping with the nature of the study as an evaluation of noninferiority.
The groups were compared with the use of analysis of variance or the Kruskal–Wallis test7 for continuous outcomes. Categorical outcomes were compared with the use of exact or asymptotic contingency-table tests and logistic regression. Unless otherwise noted, longitudinal outcomes, such as the reactogenicity of the vaccine, reflect the worst possible (most severe) outcome, rather than the best possible outcome. The statistical significance of these results was confirmed with the use of generalized estimating equations. According to the study protocol, the vaccination had to be evaluated at least once on day 7, 8, or 9 and again on day 13, 14, or 15 and could be evaluated at other follow-up visits at the discretion of the evaluators. In addition, one clinical center evaluated all vaccination sites on day 10, 11, or 12. To allow for the possibility that a small number of subjects had been exposed to vaccinia virus before the study, we analyzed the data according to the intention-to-treat principle.
No subjects were lost to follow-up. One subject who had no response to the initial vaccination was not revaccinated because of logistic constraints.
Results
Characteristics of the Subjects
A total of 680 subjects were enrolled: 106 received undiluted vaccine, 234 received a 1:5 dilution, and 340 received a 1:10 dilution. Five hundred eighty-four subjects were white (85.9 percent), 39 were black (5.7 percent), 26 were Asian (3.8 percent), 16 were Hispanic (2.4 percent), 3 were Native American (0.4 percent), 1 was a Pacific Islander (0.1 percent), and the racial or ethnic background of 11 subjects (1.6 percent) was unknown. There were 346 women (50.9 percent), and the mean (±SD) age of the subjects was 24.8±3.7 years. There were no significant differences (P=0.51 by Pearson's exact chi-square test6) in these characteristics among the groups.
Titers and Stability of Vaccine
The geometric mean titers of vaccinia virus were 108.1 pfu per milliliter in the case of undiluted vaccine (range, 107.8 to 108.4), 107.2 pfu per milliliter in the case of the 1:5 dilution (range, 106.9 to 107.5), and 106.8 pfu per milliliter in the case of the 1:10 dilution (range, 106.0 to 107.2). At 1 site two of the three vaccine preparations of the 1:10 dilution had lower titers (106.0 and 106.2 pfu per milliliter, as compared with a mean titer of 107.0 pfu per milliliter at the 12 other sites). The reason for the lower titers among 2 of 14 preparations of the 1:10 dilution of vaccine is unknown, but vaccination was successful in all the subjects who received these preparations; handling and shipping of the vaccine to the central laboratory may have led to the decrease in titer in these 2 instances. Therefore, throughout this article we use 107.0 pfu per milliliter as the mean titer for the 1:10 dilution.
To understand the amount of virus potentially delivered, we measured the number of plaque-forming units of virus on three representative bifurcated needles. The needles with undiluted vaccine had a mean of 105.0 pfu (range, 104.8 to 105.2), the needles with the 1:5 dilution of vaccine had a mean of 104.3 pfu (range, 104.1 to 104.5), and the needles with the 1:10 dilution of vaccine had a mean of 103.9 pfu (range, 103.8 to 104.1).
Assessments of the stability of the vaccinia virus demonstrated that when reconstituted in the new diluent, it remained viable, with consistent titers (within 100.3 pfu per milliliter), for seven days at 2 to 8°C. The titers of the undiluted vaccine were 107.8, 107.9, and 107.4 pfu per milliliter on day 0, on day 7, and at four months, respectively. The titers of the 1:5 dilution were 107.5, 107.2, and 106.6 pfu per milliliter on day 0, on day 7, and at four months, respectively. The titers of the 1:10 dilution were 106.9, 106.9, and 106.5 pfu per milliliter on day 0, on day 7, and at four months, respectively.
Success Rate
The initial vaccination was successful in 665 of the 680 subjects (97.8 percent). There was no significant difference in the rate of vesicle formation over the range of titers tested — 108.1, 107.2, and 107.0 pfu per milliliter (Table 1Table 1
Rate of Success of Initial and Repeated Vaccination with Vaccinia Virus.). When the results of the initial vaccination were combined with those of revaccination, the upper limit of the one-sided 95 percent confidence interval for the difference in values was 0.5 percentage point for the 1:5 dilution and 1.7 percentage points for the 1:10 dilution; thus, the noninferiority of the diluted vaccines as compared with the undiluted vaccine was established. This criterion was also achieved when the analysis included only the results of the initial vaccination (the upper limit of the one-sided confidence interval for the difference in values was 1.8 percentage points for the 1:5 dilution and 4.6 percentage points for the 1:10 dilution). The criterion was essentially met with the use of a more conservative two-sided confidence interval (data not shown), except that the upper limit of the 95 percent confidence interval for the difference in values was 5.1 percentage points for the comparison of a single vaccination of a 1:10 dilution with a single vaccination of undiluted vaccine.At three of the clinical centers, the first vaccination with each preparation was successful for every subject. All 665 subjects with a response to the first vaccination had a primary response, except 1 subject with an accelerated response4 that rapidly resolved after the first vaccination. On further questioning, this subject reported a history of international travel and vaccinia virus vaccination at the age of 16 months. At one center, 15 of 173 subjects (8.7 percent) had no response to the first vaccination. Six of these subjects (40.0 percent) had neutralizing antibodies in serum samples obtained before vaccination, in contrast to 0 of 28 randomly selected subjects in whom vaccination was successful (P<0.001 by Fisher's exact test). Fourteen of the 15 subjects were revaccinated with the same titer between 7 and 17 days after the first vaccination. The second vaccination was successful in 7 of the 14 subjects (0 of 3 given undiluted vaccine, 2 of 2 given a 1:5 dilution of vaccine, and 5 of 9 given a 1:10 dilution of vaccine).
Reactogenicity
Local signs and symptoms of vaccinia virus replication among all 665 subjects in whom the initial vaccination was successful are summarized in Table 2Table 2
Local Signs and Symptoms of Vaccinia Virus Replication among the 665 Subjects with Vesicle Formation after the First Vaccination.. The diameter of the pustule was maximal on day 13 or 14 (mean, 12.4 mm) (Figure 2AFigure 2Photographs of Primary Reactions and Common Adverse Events after Vaccination with Vaccinia Virus., Figure 2B, and Figure 2K). Erythema and induration were maximal on day 10, 11, or 12 (mean, 51.4 and 48.1 mm, respectively), then decreased rapidly (Figure 2A, Figure 2B, Figure 2I, and Figure 2J). However, some subjects had very large areas of redness and swelling. Ten percent had diameters of redness exceeding 10 cm on day 10, 11, or 12, and 50 percent had diameters of redness exceeding 4 cm. Local satellite lesions near the site of inoculation were observed in 5.8 percent of subjects on day 13 or 14 (Figure 2B and Figure 2C) and were more common among subjects who had received diluted vaccine. Regional lymphadenopathy was common, occurring in 30.5 percent of subjects on day 7, 8, or 9.The frequency and severity of systemic signs or symptoms of vaccinia virus replication and pain at the vaccination site among all 665 subjects in whom the initial vaccination was successful are summarized in Table 3Table 3
Frequency and Severity of Systemic Signs and Symptoms of Vaccinia Virus Replication and Pain among All the Subjects with Vesicle Formation after the First Vaccination.. Fever (a temperature of at least 37.7°C [100°F]) occurred in 59 of 665 subjects (8.9 percent) on day 7, 8, or 9. However, a temperature of 38.3°C (101°F) or higher was uncommon, occurring in only 20 of 665 subjects (3.0 percent) on day 7, 8, or 9. Beyond day 14, fever was recorded in only two subjects (0.3 percent). Headaches were common at all times. Severe headache was present in 14 subjects at some time during the first six days and on day 7, 8, or 9 (2.1 percent) and in 17 subjects (2.6 percent) on day 10, 11, or 12. Muscle aches and chills were also common; 137 subjects (20.6 percent) reported moderate or severe muscle aches on day 7, 8, or 9, and 43 subjects (6.5 percent) reported moderate or severe chills during this period. Moderate or severe nausea (incidence, 3.9 percent) and moderate or severe fatigue (incidence, 19.7 percent) were common on day 7, 8, or 9 after vaccination.Rashes occurred at sites other than the vaccination site in 37 subjects (5.6 percent) on day 7, 8, or 9 and in 67 subjects (10.1 percent) on day 10, 11, or 12. In all, 95 subjects (14.3 percent) had a rash (Figure 2D, Figure 2E, Figure 2F, and Figure 2G) at a site other than the vaccination site at some point during follow-up; 18 were described as moderate and 5 as severe. Pustular or vesicular rashes were the most common rash and were most commonly observed on the chest and back. The rashes resolved spontaneously in all subjects. At least two subjects had rashes that were consistent with a diagnosis of erythema multiforme (Figure 2H). Some subjects had small papules (1 to 2 mm in diameter) on the trunk (Figure 2D). These papules were not considered to represent disseminated vaccinia, and the lesions resolved in a few days without treatment.
Pain at the vaccination site was common and was moderate or severe in 225 subjects (33.8 percent) on day 7, 8, or 9 and in 202 subjects (30.4 percent) on day 10, 11, or 12. More than one third of the subjects (36.4 percent) were sufficiently ill to miss school, work, or recreational activities or to have trouble sleeping.
The differences in local signs of vaccinia virus replication after vaccination with any of the three titers of vaccine are summarized in Table 4Table 4
Differences in Local Signs of Vaccinia Virus Replication after Vaccination in 665 Subjects with Vesicle Formation after the First Vaccination.. There was no significant difference in the mean diameter of the pustule on day 13 or 14 among the three groups (P=0.10). However, subjects given undiluted vaccine had significantly larger areas of erythema (P<0.001) and induration (P=0.004) on day 7, 8, or 9 and a significantly higher incidence of regional lymphadenopathy on day 7, 8, or 9 (P=0.003) but a significantly lower incidence of satellite lesions on day 13 or 14 (P=0.003).Twelve subjects had serious adverse events, defined by the need for a visit to the clinic or emergency department or for hospitalization. Seven serious adverse events were classified as unrelated to vaccination. Two were classified as probably not related to vaccination: one case of bronchitis 12 days after vaccination and an episode of syncope 4 days after vaccination. In one subject, a high fever (temperature, 40.1°C [104.2°F]) on day 11 was classified as possibly related to the vaccine. Two serious adverse events were classified as definitely related to vaccination: one subject had a severe headache and nausea beginning five days after vaccination that resolved after day 14, and one subject had a large area of erythema (29 by 6.5 cm) around the vaccination site, which developed eight days after vaccination and had resolved by day 15.
Discussion
Our results suggest that the current stocks of vaccinia virus can be diluted to a titer of approximately 107.0 pfu per milliliter and still induce local viral replication and vesicle formation in a high proportion of persons who had never before been vaccinated. The lot of vaccine we used in our pilot study had a lower titer (107.8 pfu per milliliter), and a 1:10 dilution yielded a titer of 106.5 pfu per milliliter.2 The higher rate of response to the 1:10 dilution in the current study indicated that a titer of approximately 107.0 pfu per milliliter is needed to obtain a success rate of 95 percent or more.
Only eight subjects (1.2 percent) did not have a response after two vaccinations. Five of these eight were among the subjects who had preexisting neutralizing antibodies, suggesting that they had been vaccinated as infants. The use of a 1:10 dilution of vaccine in persons who have never been vaccinated, followed by a second vaccination in those with no response after seven days, could potentially protect nearly 10 times as many persons as would be protected by the administration of undiluted vaccine.
The rate of adverse reactions to vaccinia vaccine is dependent on age and immune status.4,5,8-16 Although there were no life-threatening adverse events, such as encephalitis or progressive vaccinia, in our study, there was a substantial degree of reactogenicity. The high frequency of local pain and erythema at the inoculation site, regional lymphadenopathy, and fever reflect active replication of vaccinia virus, with resultant acute viral illness. For the most part, the symptoms were mild to moderate. Although these adverse events were not serious, in more than one third of subjects they were the cause of missed work, school, sleep, or recreational activities. Autoinoculation of the eyes or the genitalia may occur in vaccinated children, and vaccinated persons may also inadvertently inoculate unvaccinated persons; we avoided these potentially serious events by applying semipermeable-membrane bandages to the inoculation sites.
There were significant differences in the incidence of local reactions between the group given undiluted vaccine and the groups given diluted vaccine. Undiluted vaccine resulted in larger areas of inflammation and a higher incidence of regional lymphadenopathy, whereas diluted vaccine resulted in a higher incidence of satellite lesions. These two observations may be related; increased inflammation may limit viral replication and therefore reduce the formation of local satellite lesions in persons who receive a high-titer vaccine. These clinical observations are also consistent with the observation in the pilot study that, although all subjects in whom vaccination was successful had cellular immune responses, the responses were more vigorous in the group that received undiluted vaccine. Whether or not the increased local inflammation associated with undiluted vaccine is due to a more rapid rate of replication soon after vaccination or to the inoculation of a minor subpopulation of more virulent vaccinia is not known. The morphology of vaccinia virus plaques in tissue culture is highly variable, suggesting that a mixed population of virus is present in the vaccine.
Whether or not persons vaccinated more than 30 years previously can be successfully revaccinated with diluted vaccine (e.g., doses as low as 107.0 pfu per milliliter) remains to be determined. Our observation that 6 of 14 subjects with no response after the initial vaccination had preexisting neutralizing antibodies suggests that the success rates in this population may be lower. Studies are being designed to determine whether protection is associated with preexisting antibody levels, cellular immunity, or both and whether a significant boost in immunity can occur in the absence of a primary response to vaccination.
Supported by contracts with the National Institute of Allergy and Infectious Diseases (N01-AI-45150, N01-AI-45248, N01-AI-45257, N01-AI-85342, N01-AI-65298, and N01-AI-15448) and by a contract from the National Center for Research Resources (M01-RR00188).
This article was published at www.nejm.org on March 28, 2002.
We are indebted to John Becher and Lisa Rotz at the Centers for Disease Control and Prevention for their assistance and thoughtful discussions; to Elizabeth Beim and the entire Emmes staff for their support of the protocol; to Edwin Anderson, M.D., Dennis Cunningham, M.D., James D. Campbell, M.D., Karen Kotloff, M.D., Genevieve Losonsky, M.D., Steven S. Wasserman, Ph.D., Michele Trucksis, Ph.D., M.D., Paul S. Sehdev, M.D., Michael Keefer, M.D., Robert Betts, M.D., Jeff Laduca, M.D., Thomas R. Cate, M.D., Ramona Simionescu, M.D., and Deep Ajmani, M.D., for their clinical assistance; and to the staff at the clinical sites.
Source Information
From the Department of Medicine, National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit, Saint Louis University School of Medicine, St. Louis (S.E.F., F.K.N., R.B.B.); the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston (R.B.C., R.L.A.); the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore (C.O.T., R.E.); the University of Rochester School of Medicine and Dentistry, Rochester, N.Y. (J.J.T., C.M.N.); and the Emmes Corporation, Rockville, Md. (M.W.).
Address reprint requests to Dr. Belshe at the Division of Infectious Diseases and Immunology, Saint Louis University Health Sciences Center, 3635 Vista Ave. (FDT-8N), St. Louis, MO 63110.
Appendix
In addition to the authors, the National Institute of Allergy and Infectious Diseases Smallpox Vaccine Study Group includes Stephen P. Heyse, M.D., M.P.H., Holli Hamilton, M.D., M.P.H., Pamela McInnes, D.D.S., Walla Dempsey, Ph.D., Lydia Falk, Ph.D., and Wendy Fanaroff-Ravick, R.N., M.S.N., all of the National Institute of Allergy and Infectious Diseases, Bethesda, Md.
- References
References
1
Henderson DA . The looming threat of bioterrorism. Science 1999;283:1279-1282
CrossRef | Web of Science | Medline2
Frey SE ,Newman FK ,Cruz J , et al. Dose-related effects of smallpox vaccine. N Engl J Med 2002;346:1275-1280
Full Text | Web of Science | Medline3
Katz JB . The effect of the virus-serum incubation period upon vaccinia virus serum neutralization titers. J Biol Stand 1987;15:389-392
CrossRef | Medline4
Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Morb Mortal Wkly Rep 2001;50:1-25
Medline5
Graham BS ,Belshe RB ,Clements ML , et al. Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. J Infect Dis 1992;166:244-252
CrossRef | Web of Science | Medline6
StatXact-3 for Windows: statistical software for exact nonparametric inference. Cambridge, Mass.: CYTEL Software, 1995.
7
Holander M, Wolfe D. Nonparametric statistical methods. New York: John Wiley, 1973:115-6.
8
Lane JM ,Ruben FL ,Neff JM ,Millar JD . Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis 1970;122:303-309
CrossRef | Web of Science | Medline9
Fulginiti VA ,Kempe CH ,Hathaway WE , et al. Progressive vaccinia in immunologically-deficient individuals. Birth Defects Orig Artic Ser 1968;5:129-12910
O'Connell CJ ,Karzon DT ,Barron AL ,Plaut ME ,Ali VM . Progressive vaccinia with normal antibodies: a case possibly due to deficient cellular immunity. Ann Intern Med 1964;60:282-289
Web of Science | Medline11
Redfield RR ,Wright DC ,James WD ,Jones TS ,Brown C ,Burke DS . Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987;316:673-676
Full Text | Web of Science | Medline12
Freed ER ,Duma RJ ,Escobar MR . Vaccinia necrosum and its relationship to impaired immunologic responsiveness. Am J Med 1972;52:411-420
CrossRef | Web of Science | Medline13
Feery BJ . Adverse reactions after smallpox vaccination. Med J Aust 1977;2:180-183
Web of Science | Medline14
Connor JD ,McIntosh K ,Cherry JD , et al. Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration: primary subcutaneous vaccination. J Infect Dis 1977;135:167-175
CrossRef | Web of Science | Medline15
Cherry JD ,McIntosh K ,Connor JD , et al. Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration: primary percutaneous vaccination. J Infect Dis 1977;135:145-154
CrossRef | Web of Science | Medline16
Sinclair MC ,Lane JM ,Donald WJ ,Esco LC . Complications of smallpox vaccination in Alabama, 1968. South Med J 1972;65:41-44
CrossRef | Web of Science | Medline
- Citing Articles (101)
Citing Articles
1
J. S. Kennedy, M. Gurwith, C. L. Dekker, S. E. Frey, K. M. Edwards, J. Kenner, M. Lock, C. Empig, S. Morikawa, M. Saijo, H. Yokote, K. Karem, I. Damon, M. Perlroth, R. N. Greenberg. (2011) Safety and Immunogenicity of LC16m8, an Attenuated Smallpox Vaccine in Vaccinia-Naive Adults. Journal of Infectious Diseases 204:9, 1395-1402
CrossRef2
Gary Hermanson, Sookhee Chun, Jiin Felgner, Xiaolin Tan, Jozelyn Pablo, Rie Nakajima-Sasaki, Douglas M. Molina, Philip L. Felgner, Xiaowu Liang, D. Huw Davies. (2011) Measurement of antibody responses to Modified Vaccinia virus Ankara (MVA) and Dryvax® using proteome microarrays and development of recombinant protein ELISAs. Vaccine
CrossRef3
Sarah E. Church, Shawn M. Jensen, Christopher G. Twitty, Keith Bahjat, Hong-Ming Hu, Walter J. Urba, Bernard A. Fox. (2011) Multiple Vaccinations. The Cancer Journal 17:5, 379-396
CrossRef4
Stephen R Walsh, Raphael Dolin. (2011) Vaccinia viruses: vaccines against smallpox and vectors against infectious diseases and tumors. Expert Review of Vaccines 10:8, 1221-1240
CrossRef5
S. S. Ahmed, S. A. Plotkin, S. Black, R. L. Coffman. (2011) Assessing the Safety of Adjuvanted Vaccines. Science Translational Medicine 3:93, 93rv2-93rv2
CrossRef6
M. Susan Lewis-Jones. 2011. Poxviruses. , 51.1-51.25.
CrossRef7
Aklile Berhanu, David S. King, Stacie Mosier, Robert Jordan, Kevin F. Jones, Dennis E. Hruby, Douglas W. Grosenbach. (2010) Impact of ST-246® on ACAM2000™ smallpox vaccine reactogenicity, immunogenicity, and protective efficacy in immunodeficient mice. Vaccine 29:2, 289-303
CrossRef8
Hee-Chang Jang, Choong Jong Kim, Kye Hyoung Kim, Kwang-Hee Lee, Young-Ho Byun, Baik-Lin Seong, Giulietta Saletti, Cecil Czerkinsky, Wan Beom Park, Sang-Won Park, Hong-Bin Kim, Nam Joong Kim, Myoung-don Oh. (2010) A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers. Vaccine 28:36, 5845-5849
CrossRef9
Bénédicte Puissant-Lubrano, Philippe Bossi, Frederick Gay, Jean-Marc Crance, Olivia Bonduelle, Daniel Garin, François Bricaire, Brigitte Autran, Behazine Combadière. (2010) Control of vaccinia virus skin lesions by long-term-maintained IFN-γ+TNF-α+ effector/memory CD4+ lymphocytes in humans. Journal of Clinical Investigation 120:5, 1636-1644
CrossRef10
S. M. Breathnach, C. H. Smith, R. J. G. Chalmers, R. J. Hay. 2010. Systemic Therapy. , 1-53.
CrossRef11
Alfred von Krempelhuber, Jens Vollmar, Rolf Pokorny, Petra Rapp, Niels Wulff, Barbara Petzold, Amanda Handley, Lyn Mateo, Henriette Siersbol, Herwig Kollaritsch, Paul Chaplin. (2010) A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®. Vaccine 28:5, 1209-1216
CrossRef12
Philippe Bossi. 2009. National and International Aspects on Bioterrorism and Biosecurity. .
CrossRef13
Richard B. Kennedy, Inna Ovsyannikova, Gregory A. Poland. (2009) Smallpox vaccines for biodefense. Vaccine 27, D73-D79
CrossRef14
H. G. Welch, P. C. Albertsen. (2009) Prostate Cancer Diagnosis and Treatment After the Introduction of Prostate-Specific Antigen Screening: 1986-2005. JNCI Journal of the National Cancer Institute 101:19, 1325-1329
CrossRef15
Richard B Kennedy, Inna G Ovsyannikova, Robert M Jacobson, Gregory A Poland. (2009) The immunology of smallpox vaccines. Current Opinion in Immunology 21:3, 314-320
CrossRef16
Gregory A Poland, Inna G Ovsyannikova, Robert M Jacobson. (2009) Application of pharmacogenomics to vaccines. Pharmacogenomics 10:5, 837-852
CrossRef17
Emilia Anis, Alex Leventhal, Paul E. Slater, Eilat Shinar, Vered Yahalom, Zahava Smetana, Ruth Zach, Shmuel Reznikovich, Ella Mendelson, Yehuda Danon, Boaz Lev. (2009) Smallpox revaccination of 21000 first responders in Israel: lessons learned. International Journal of Infectious Diseases 13:3, 403-409
CrossRef18
Stephen J. Thomas, Joachim Hombach, Alan Barrett. (2009) Scientific consultation on cell mediated immunity (CMI) in dengue and dengue vaccine development. Vaccine 27:3, 355-368
CrossRef19
Andrew W. Artenstein. (2008) New generation smallpox vaccines: a review of preclinical and clinical data. Reviews in Medical Virology 18:4, 217-231
CrossRef20
Richard N Greenberg, Jeffrey S Kennedy. (2008) ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine. Expert Opinion on Investigational Drugs 17:4, 555-564
CrossRef21
Raymond A. Strikas, Linda J. Neff, Lisa Rotz, Joanne Cono, Donna Knutson, Joseph Henderson, Walter A. Orenstein. (2008) US Civilian Smallpox Preparedness and Response Program, 2003. Clinical Infectious Diseases 46:s3, S157-S167
CrossRef22
David L. Swerdlow, Martha H. Roper, Juliette Morgan, Richard A. Schieber, Laurence S. Sperling, Mercedes M. Sniadack, Linda Neff, Jacqueline W. Miller, Christine R. Curtis, Mona E. Marin, John Iskander, Pedro Moro, Paige Hightower, Nancy H. Levine, Mary McCauley, James Heffelfinger, Inger Damon, Thomas J. Török, Melinda Wharton, Eric E. Mast, Gina T. Mootrey, . (2008) Ischemic Cardiac Events during the Department of Health and Human Services Smallpox Vaccination Program, 2003. Clinical Infectious Diseases 46:s3, S234-S241
CrossRef23
Kathleen A. Marriott, Christopher V. Parkinson, Samantha I. Morefield, Robert Davenport, Richard Nichols, Thomas P. Monath. (2008) Clonal vaccinia virus grown in cell culture fully protects monkeys from lethal monkeypox challenge. Vaccine 26:4, 581-588
CrossRef24
Melamed Sharon, Paran Nir, Katz Lior, Ben-Nathan David, Israely Tomer, Schneider Paula, Levin Reuven, Lustig Shlomo. (2007) Tail scarification with Vaccinia virus Lister as a model for evaluation of smallpox vaccine potency in mice. Vaccine 25:45, 7743-7753
CrossRef25
Pragati Nigam, Patricia L. Earl, Jeffrey L. Americo, Sunita Sharma, Linda S. Wyatt, Yvette Edghill-Spano, Lakshmi S. Chennareddi, Peter Silvera, Bernard Moss, Harriet L. Robinson, Rama Rao Amara. (2007) DNA/MVA HIV-1/AIDS vaccine elicits long-lived vaccinia virus-specific immunity and confers protection against a lethal monkeypox challenge. Virology 366:1, 73-83
CrossRef26
Patricia Nell, Katrin S. Kohl, Philip L. Graham, Philip S. LaRussa, S. Michael Marcy, Vincent A. Fulginiti, Bryan Martin, Ingrid Trolin, Scott A. Norton, John M. Neff. (2007) Eczema vaccinatum as an adverse event following exposure to vaccinia virus: Case definition & guidelines of data collection, analysis, and presentation of immunization safety data. Vaccine 25:31, 5725-5734
CrossRef27
N. D. Ostrout, M. M. McHugh, D. J. Tisch, A. M. Moormann, V. Brusic, J. W. Kazura. (2007) Long-term T cell memory to human leucocyte antigen-A2 supertype epitopes in humans vaccinated against smallpox. Clinical & Experimental Immunology 149:2, 265-273
CrossRef28
Patricia Nell, Katrin S. Kohl, Philip L. Graham, Philip S. LaRussa, S. Michael Marcy, Vincent A. Fulginiti, Bryan Martin, Ann McMahon, Scott A. Norton, Ingrid Trolin. (2007) Progressive vaccinia as an adverse event following exposure to vaccinia virus: Case definition and guidelines of data collection, analysis, and presentation of immunization safety data. Vaccine 25:31, 5735-5744
CrossRef29
Philip L. Graham, Philip S. LaRussa, Katrin S. Kohl. (2007) Robust take following exposure to vaccinia virus: Case definition and guidelines of data collection, analysis, and presentation of immunization safety data. Vaccine 25:31, 5763-5770
CrossRef30
Peter Wenger, James M. Oleske, Katrin S. Kohl, Margaret C. Fisher, James H. Brien, Philip L. Graham, Philip S. LaRussa, Susan Lipton, Bruce Tierney. (2007) Inadvertent inoculation as an adverse event following exposure to vaccinia virus: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 25:31, 5754-5762
CrossRef31
John Beigel, Katrin S. Kohl, Floyd Brinley, Philip L. Graham, Najwa Khuri-Bulos, Philip S. LaRussa, Patricia Nell, Scott Norton, Gillian Stoltman, Amina Tebaa, Karen Warschaw. (2007) Generalized vaccinia as an adverse event following exposure to vaccinia virus: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 25:31, 5745-5753
CrossRef32
Wolfram Metzger, Benjamin G Mordmueller, Wolfram Metzger. 2007. Vaccines for preventing smallpox. .
CrossRef33
Stephen R. Walsh, R. Paul Johnson. (2007) Vaccinia Folliculitis After Primary Dryvax Vaccination. Infectious Diseases in Clinical Practice 15:2, 132-134
CrossRef34
N. R. Attard, B. D. De Silva. (2007) Erythema multiforme associated with resolving molluscum contagiosum. Clinical and Experimental Dermatology 32:2, 214-215
CrossRef35
David C Tscharke. (2007) Adaptive immunity to vaccinia virus: revisiting an old friend. Future Virology 2:2, 163-172
CrossRef36
Virginia L Kan, Jody Manischewitz, Lisa R King, Hana Golding. (2007) Durable neutralizing antibodies after remote smallpox vaccination among adults with and without HIV infection. AIDS 21:4, 521-524
CrossRef37
Itay Wiser, Ran D. Balicer, Dani Cohen. (2007) An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies. Vaccine 25:6, 976-984
CrossRef38
John Treanor, Hulin Wu, Hua Liang, David J. Topham. (2006) Immune responses to vaccinia and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults. Vaccine 24:47-48, 6913-6923
CrossRef39
Stephen K. Obaro, Martin O. Ota. (2006) Sense and the science of childhood immunization: Can we achieve more with less?. Vaccine 24:42-43, 6460-6467
CrossRef40
Robert Jordan, Dennis Hruby. (2006) Smallpox antiviral drug development: satisfying the animal efficacy rule. Expert Review of Anti-infective Therapy 4:2, 277-289
CrossRef41
David B. Cohen, Alethia H. Cook. (2006) At the Intersection of Public Health and National Security: The Evolution of Smallpox Policy in the Clinton and G.W. Bush Administrations. Politics & Policy 34:1, 156-194
CrossRef42
Jens Vollmar, Nathaly Arndtz, Karl M. Eckl, Torben Thomsen, Barbara Petzold, Luis Mateo, Bernd Schlereth, Amanda Handley, Lynette King, Vanessa Hülsemann, Maria Tzatzaris, Karin Merkl, Niels Wulff, Paul Chaplin. (2006) Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine. Vaccine 24:12, 2065-2070
CrossRef43
K. H. Waibel, H. Golding, J. Manischewitz, L. R. King, M. Tuchscherer, R. L. Topolski, D. S. Walsh. (2006) Clinical and Immunological Comparison of Smallpox Vaccine Administered to the Outer versus the Inner Upper Arms of Vaccinia-Naive Adults. Clinical Infectious Diseases 42:4, e16-e20
CrossRef44
Kemba N. Lee, Christina L. Hutson, Richard Kline, Aaron T. Curns, Cindy Dougherty, Chris Allen, Inger Damon, Russell Regnery. (2006) Smallpox vaccine stability after maintenance at temperatures not recommended for shipping. Vaccine 24:7, 884-886
CrossRef45
Zack S Moore, Jane F Seward, J Michael Lane. (2006) Smallpox. The Lancet 367:9508, 425-435
CrossRef46
Daniel S Hamilton, Bradley T Smith. (2006) Atlantic Storm. EMBO reports 7:1, 4-9
CrossRef47
S NAFZIGER. (2005) Smallpox. Critical Care Clinics 21:4, 739-746
CrossRef48
Richard L. Kline, Russell L. Regnery, Gregory L. Armstrong, Inger K. Damon. (2005) Stability of diluted smallpox vaccine under simulated clinical conditions. Vaccine 23:41, 4944-4946
CrossRef49
Stuart S. Olmsted, John D. Grabenstein, Arvind K. Jain, William Comerford, Pamela Giambo, Pamela Johnson, Judie Mopsik, S. Rebecca Zimmerman, Nicole Lurie. (2005) Use of an Electronic Monitoring System for Self-Reporting Smallpox Vaccine Reactions. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 3:3, 198-206
CrossRef50
Cressida Auckland, Alexandra Cowlishaw, Dilys Morgan, Elizabeth Miller. (2005) Reactions to small pox vaccine in naïve and previously-vaccinated individuals. Vaccine 23:32, 4185-4187
CrossRef51
Andrew W. Artenstein, Casey Johnson, Thomas C. Marbury, Dennis Morrison, Paul S. Blum, Tracy Kemp, Richard Nichols, John P. Balser, Michelle Currie, Thomas P. Monath. (2005) A novel, cell culture-derived smallpox vaccine in vaccinia-naïve adults. Vaccine 23:25, 3301-3309
CrossRef52
James Baggs, Robert T. Chen, Inger K. Damon, Lisa Rotz, Christopher Allen, Kathleen E. Fullerton, Christine Casey, Dale Nordenberg, Gina Mootrey. (2005) Safety Profile of Smallpox Vaccine: Insights from the Laboratory Worker Smallpox Vaccination Program. Clinical Infectious Diseases 40:8, 1133-1140
CrossRef53
Jacquelyn J. Bower, Xianglin Shi. (2005) Environmental Health Research in the Post-Genome Era: New Fields, New Challenges, and New Opportunities. Journal of Toxicology and Environmental Health, Part B 8:2, 71-94
CrossRef54
Charles J. Hackett, Daniel Rotrosen, Marshall Plaut. (2005) Addressing challenges for allergists in vaccination to protect against smallpox. Annals of Allergy, Asthma & Immunology 94:1, 1-3
CrossRef55
James Sejvar, Roumiana Boneva, J. Michael Lane, John Iskander. (2005) Severe Headaches Following Smallpox Vaccination. Headache: The Journal of Head and Face Pain 45:1, 87-88
CrossRef56
Manoj Karwa, Brian Currie, Vladmir Kvetan. (2005) Bioterrorism: Preparing for the impossible or the improbable. Critical Care Medicine 33:Supplement, S75-S95
CrossRef57
Richard N Greenberg, Jeffrey S Kennedy, David J Clanton, Elizabeth A Plummer, Lynda Hague, John Cruz, Francis A Ennis, William C Blackwelder, Robert J Hopkins. (2005) Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial. The Lancet 365:9457, 398-409
CrossRef58
2004. Meeting the Needs of Children. .
CrossRef59
2004. Psychological Factors in Patients and the Public. .
CrossRef60
Claudia Vellozzi, Francisco Averhoff, J. Michael Lane, Xiaojun Wen, Anne C. Moore, Scott Santibanez, Andrew Kroger, La Mar Hasbrouck, Allison Kennedy, Christine G. Casey. (2004) Superinfection Following Smallpox Vaccination (Vaccinia), United States: Surveillance January 2003 through January 2004. Clinical Infectious Diseases 39:11, 1660-1666
CrossRef61
Thomas P. Monath, Joseph R. Caldwell, Wolfgang Mundt, Joan Fusco, Casey S. Johnson, Mark Buller, Jian Liu, Bridget Gardner, Greg Downing, Paul S. Blum, Tracy Kemp, Richard Nichols, Richard Weltzin. (2004) ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain) – a second-generation smallpox vaccine for biological defense. International Journal of Infectious Diseases 8, 31-44
CrossRef62
Jason A. Regules, David P. Dooley, Matthew J. Hepburn, David A. Van De Car, Kepler A. Davis, Kenneth C. McAllister, Duane R. Hospenthal, Clinton K. Murray, Rajat Fofaria, John R. Ekstrand, Helen K. Crouch. (2004) The effect of semipermeable dressings on smallpox vaccine site evolution. American Journal of Infection Control 32:6, 333-336
CrossRef63
R. J. Hopkins, J. M. Lane. (2004) Clinical Efficacy of Intramuscular Vaccinia Immune Globulin: A Literature Review. Clinical Infectious Diseases 39:6, 819-826
CrossRef64
Ashish Chopra, Lisa A. Drage, Eric M. Hanson, Nicole L. Touchet. (2004) Stevens-Johnson Syndrome After Immunization With Smallpox, Anthrax, and Tetanus Vaccines. Mayo Clinic Proceedings 79:9, 1193-1196
CrossRef65
A. Chopra, L. A. Drage, E. M. Hanson, N. L. Touchet. (2004) Stevens-Johnson Syndrome After Immunization With Smallpox, Anthrax, and Tetanus Vaccines. Mayo Clinic Proceedings 79:9, 1193-1196
CrossRef66
Spuls Phyllis I., Bos Jan D., Rudikoff Donald. (2004) Smallpox: What the Dermatologist Should Know. SKINmed 3:4, 197-208
CrossRef67
Ana Martin‐Ancel, Maria Luisa Casas, Bartolome Bonet. (2004) Implications of Postvaccination Hepatitis B Surface Antigenemia in the Management of Exposures to Body Fluids • . Infection Control and Hospital Epidemiology 25:7, 611-613
CrossRef68
Catherine Sartor, Philippe Brunet, Sophie Simon, Catherine Tamalet, Yvon Berland, Michel Drancourt. (2004) Transmission of Hepatitis C Virus Between Hemodialysis Patients Sharing the Same Machine • . Infection Control and Hospital Epidemiology 25:7, 609-611
CrossRef69
Georgia Thomas, Elizabeth Frenzel, Hend Hanna. (2004) Smallpox Vaccine: “Non‐Take” Responses in Previously Vaccinated Adults • . Infection Control and Hospital Epidemiology 25:7, 613-615
CrossRef70
Anne C. Moore, Adrian V. S. Hill. (2004) Progress in DNA-based heterologous prime-boost immunization strategies for malaria. Immunological Reviews 199:1, 126-143
CrossRef71
R. B Quigley. (2004) Uncertain Benefit: The Public Policy of Approving Smallpox Vaccine Research. American Journal of Public Health 94:6, 943-947
CrossRef72
D. A. Salmon, L. H. Moulton, N. A. Halsey. (2004) Enhancing Public Confidence in Vaccines Through Independent Oversight of Postlicensure Vaccine Safety. American Journal of Public Health 94:6, 947-950
CrossRef73
Morad Hassani, Mahesh C Patel, Liise-anne Pirofski. (2004) Vaccines for the prevention of diseases caused by potential bioweapons. Clinical Immunology 111:1, 1-15
CrossRef74
Richard N. Greenberg, Robert H. Schosser, Elizabeth A. Plummer, Sara E. Roberts, Malissia A. Caldwell, Dana L. Hargis, David W. Rudy, Martin E. Evans, Robert J. Hopkins. (2004) Urticaria, Exanthems, and Other Benign Dermatologic Reactions to Smallpox Vaccination in Adults. Clinical Infectious Diseases 38:7, 958-965
CrossRef75
Rosemary K. Sokas, Dennis M. Perrotta. (2003) Preparedness: Where is Occupational and Environmental Health?. Journal of Occupational and Environmental Medicine 45:11, 1133-1135
CrossRef76
Julie Milstien. (2003) Emergency response vaccines: lessons learned in response to communicable diseases. Expert Opinion on Biological Therapy 3:7, 1121-1131
CrossRef77
Raffaele D’Amelio, Roberto Biselli, Sergio Natalicchio, Florigio Lista, Mario S. Peragallo. (2003) Vaccination programmes in the Italian military. Vaccine 21:25-26, 3530-3533
CrossRef78
V. A. Fulginiti, A. Papier, J. M. Lane, J. M. Neff, D. A. Henderson, D. A. Henderson, T. V. Inglesby, T. O'Toole. (2003) Smallpox Vaccination: A Review, Part I. Background, Vaccination Technique, Normal Vaccination and Revaccination, and Expected Normal Reactions. Clinical Infectious Diseases 37:2, 241-250
CrossRef79
Robert S. Baltimore, Hal B. Jenson. (2003) Should smallpox vaccine be tested in children?. Current Opinion in Infectious Diseases 16:3, 237-239
CrossRef80
C. L. Cherry, M. A. Kainer, T. A. Ruff. (2003) Biological weapons preparedness: the role of physicians. Internal Medicine Journal 33:5-6, 242-253
CrossRef81
John Bartlett, Luciana Borio, Lew Radonovich, Julie Samia Mair, Tara O’Toole, Michael Mair, Neil Halsey, Robert Grow, Thomas V. Inglesby. (2003) Smallpox Vaccination in 2003: Key Information for Clinicians. Clinical Infectious Diseases 36:7, 883-902
CrossRef82
Mike Bray. (2003) Pathogenesis and potential antiviral therapy of complications of smallpox vaccination. Antiviral Research 58:2, 101-114
CrossRef83
M KARWA, P BRONZERT, V KVETAN. (2003) Bioterrorism and critical care. Critical Care Clinics 19:2, 279-313
CrossRef84
Mike Bray, Mary E. Wright. (2003) Progressive Vaccinia. Clinical Infectious Diseases 36:6, 766-774
CrossRef85
Colleen M. Terriff, Mike D. Schwartz, Ben M. Lomaestro. (2003) Bioterrorism: Pivotal Clinical Issues. Pharmacotherapy 23:3, 274-290
CrossRef86
Derrick Baxby. (2003) Smallpox vaccination techniques. Vaccine 21:13-14, 1382-1390
CrossRef87
Michael Mair, Luciana Borio. (2003) Key Information Regarding Smallpox Vaccine. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 1:1, 53-54
CrossRef88
Anthony S. Fauci. (2003) Biodefence on the research agenda. Nature 421:6925, 787-787
CrossRef89
B.W.J Mahy. (2003) An overview on the use of a viral pathogen as a bioterrorism agent: why smallpox?. Antiviral Research 57:1-2, 1-5
CrossRef90
William Bicknell, Kenneth James. (2003) The new cell culture smallpox vaccine should be offered to the general population. Reviews in Medical Virology 13:1, 5-15
CrossRef91
Larry I Lutwick, Mary Beth Nierengarten. (2002) Vaccines for Category A bioterrorism diseases. Expert Opinion on Biological Therapy 2:8, 883-893
CrossRef92
David GE Caldicott, Nicholas A Edwards. (2002) The tools of the trade: Weapons of mass destruction. Emergency Medicine Australasia 14:3, 240-248
CrossRef93
Tener Goodwin Veenema. (2002) The Smallpox Vaccine Debate. AJN, American Journal of Nursing 102:9, 33-39
CrossRef94
Rebecca Katz. (2002) Public health preparedness: The best defense against biological weapons. The Washington Quarterly 25:3, 69-82
CrossRef95
(2002) Smallpox and Smallpox Vaccination. New England Journal of Medicine 347:9, 691-692
Full Text96
(2002) Responses to Smallpox Vaccine. New England Journal of Medicine 347:9, 689-690
Full Text97
Kevin P. O’Connell, Bernadette C. Menuey, Dawn Foster. (2002) Issues in Preparedness for Biologic Terrorism: A Perspective for Critical Care Nursing. AACN Clinical Issues: Advanced Practice in Acute and Critical Care 13:3, 452-469
CrossRef98
Robert S. Baltimore, Julia A. McMillan. (2002) Smallpox and the smallpox vaccine controversy. The Pediatric Infectious Disease Journal 21:8, 789-790
CrossRef99
P. Varkey, G. A. Poland, F. R. Cockerill, T. F. Smith, P. T. Hagen. (2002) Confronting Bioterrorism: Physicians on the Front Line. Mayo Clinic Proceedings 77:7, 661-672
CrossRef100
Breman, Joel G., Henderson, D.A., . (2002) Diagnosis and Management of Smallpox. New England Journal of Medicine 346:17, 1300-1308
Full Text101
Fauci, Anthony S., . (2002) Smallpox Vaccination Policy — The Need for Dialogue. New England Journal of Medicine 346:17, 1319-1320
Full Text
- Letters
