Correspondence

Influenza Immunization in Pregnancy — Antibody Responses in Mothers and Infants

N Engl J Med 2010; 362:1644-1646April 29, 2010

Article

To the Editor:

Though the use of seasonal trivalent inactivated influenza vaccines is recommended in pregnancy, there are few data on the immunogenicity of current vaccine formulations in pregnant women or on the duration of passive protection in their infants.1 We present antibody data for mothers and infants from a prospective, randomized, controlled trial of influenza vaccine in pregnant women,2 the Mother'sGift project.

In brief, 340 Bangladeshi women in the third trimester of pregnancy were randomly assigned to receive either a current commercial trivalent inactivated influenza vaccine (with these mothers and their infants called vaccinees) or a control (23-valent pneumococcal polysaccharide) vaccine (with these mothers and their infants called controls). Serum samples were obtained from 311 mothers before immunization and at delivery and from 292 infants at birth (cord-serum samples) and at 10 and 20 to 26 weeks later. The samples were tested with the use of hemagglutination-inhibition assays for the three virus subtypes present in the influenza vaccine: A/New Caledonia (H1N1), A/Fujian (H3N2), and B/Hong Kong (see the Supplementary Appendix, available with the full text of this letter at NEJM.org).

We report four types of data: first the geometric mean titer of the hemagglutination-inhibition antibody; second, immunogenicity, measured as the geometric mean factor increase in titer after vaccination as compared with beforehand, and also as the rate of seroconversion — either a prevaccination hemagglutination-inhibition titer of 1:10 or lower and a postvaccination titer of 1:40 or greater, or a prevaccination titer of greater than 1:10 and an increase in the titer by a factor of 4; third, seroprotection rate: the proportion of mothers and infants with protective antibody titers, defined as a hemagglutination-inhibition titer of 1:40 or more3; and fourth, the transplacental transfer of antibody, defined as the geometric mean ratio of the hemagglutination-inhibition titers in infants and mothers at the time of delivery.

Table 1Table 1Geometric Mean Titers of Hemagglutination-Inhibition Antibody in Mothers and Infants, According to Time of Sampling and Vaccine Group. lists the geometric mean titers of the hemagglutination-inhibition antibody in all groups tested. Among the mothers, the influenza vaccine subtypes A/New Caledonia (H1N1) and A/Fujian (H3N2) had greater immunogenicity (geometric mean factor increase in titer, 17.7 and 5.4, respectively, with geometric mean titers at delivery, 166.0 and 392.2, respectively) than the B/Hong Kong subtype (geometric mean factor increase in titer, 3.5; geometric mean titer, 26.0) (Table 2Table 2Vaccine Immunogenicity, Rate of Seroconversion among Mothers, and Transplacental Transfer of Hemagglutination-Inhibition Antibody, According to Vaccine Group.), as previously reported.4,5 The geometric mean ratio of the antibody titers in infants and mothers at the time of delivery ranged from 0.7 to 1.7 among vaccinees and controls. The proportion of mothers with a protective antibody titer at the time of delivery was 88% for the A/New Caledonia (H1N1) subtype and 98% for the A/Fujian (H3N2) subtype, as compared with 45% for the B/Hong Kong subtype. Similar proportions of infants had a protective antibody titer at birth (Figure 1Figure 1Proportions of Immunized Mothers and Their Infants with Hemagglutination-Inhibition (HAI) Titer of 1:40 or Greater.). In infants at birth, the ratio of the geometric mean antibody titers in cord-serum specimens among vaccinees and among controls was 22.5 for the A/New Caledonia (H1N1) antigen, 4.4 for the A/Fujian (H3N2) antigen, and 4.2 for the B/Hong Kong antigen (Table 1). In infants at 20 weeks, the ratio of the geometric mean antibody titers among vaccinees and among controls was 2.2 for A/New Caledonia (H1N1), 2.1 for A/Fujian (H3N2), and 1.0 for the B/Hong Kong (Table 1).

Among infants at 10 weeks of age, 61% and 93% had hemagglutination-inhibition titers of 1:40 or greater against the A/New Caledonia (H1N1) and A/Fujian (H3N2) subtypes, respectively, and 9% against the B/Hong Kong subtype. At 20 weeks, the percentages of infant vaccinees who had a protective hemagglutination-inhibition titer were 18% for the A/New Caledonia (H1N1) subtype and 46% for the A/Fujian (H3N2) subtype, 2 and 13 times the percentage of infant controls, respectively. The proportion of infants who had seroprotection against the B/Hong Kong antigen was not significantly different from that of infant controls. Among all the infant vaccinees, the estimated half-life of passively acquired maternal antibody against all subtypes of the influenza vaccine ranged from 42 to 50 days (95% confidence interval, 37 to 56).

These observations suggest that maternal immunization results in the presences of antibody titers against influenza A vaccine subtypes in a high proportion of mothers and their newborns. Our 6-month follow-up data show that passively acquired protective levels of serum antibody for A subtypes may be significantly greater in vaccinees than in controls up to 20 weeks of age.

Mark C. Steinhoff, M.D.
Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Saad B. Omer, M.B., B.S., Ph.D.
Emory University Rollins School of Public Health, Atlanta, GA

Eliza Roy, D.C.H.
Shams E. Arifeen, M.B., B.S., Dr.P.H.
Rubhana Raqib, Ph.D.
International Centre for Diarrheal Disease Research, Dhaka, Bangladesh

Mekibib Altaye, Ph.D.
Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Robert F. Breiman, M.D.
U.S. Centers for Disease Control and Prevention, Nairobi, Kenya

Khalequ Zaman, M.B.,B.S., M.B.,B.S., Ph.D.
International Centre for Diarrheal Disease Research, Dhaka, Bangladesh

Supported by the Bill and Melinda Gates Foundation, a cooperative agreement (HRN-A-0096-90006-00) with the U.S. Agency for International Development, the Department of Health and Human Services, the National Vaccine Program Office, Wyeth Pharmaceuticals, the Thrasher Research Fund, Aventis Pasteur, the International Centre for Diarrheal Disease Research, and the Johns Hopkins Bloomberg School of Public Health.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

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