A double-dose of inactivated influenza vaccine may not increase the immunogenicity of the vaccine among pregnant women with HIV to levels similar to those in pregnant women without HIV, according to study results published in The Lancet HIV.

To date, one randomized clinical trial has been conducted to evaluate the efficacy of the influenza vaccine to protect infants born to women with HIV who received the vaccination while pregnant. The results of this study, conducted in South Africa in 2011, showed that infants born to women with HIV do not have vaccine-induced protection, as a result of their mothers’ modest immune response to inactivated influenza vaccine (41% seroconversion after vaccination compared with 92% among pregnant women without HIV).

Researchers hypothesized that administering a second dose of vaccine or increasing the vaccine’s antigen content may improve the immunogenicity of inactivated influenza vaccine in pregnant women with HIV and vaccine-induced protection in their infants. Therefore, researched conducted a study with the objective to evaluate the immunogenicity and safety of various dosing schedules of inactivated influenza vaccine in pregnant women with HIV in South Africa.

In this double-blind, randomized, controlled study, researchers screened 800 pregnant women with HIV from 7 clinics in South Africa. Women in study cohort were aged 18 to 38 years and had an estimated gestational age of 12 to 36 weeks. Patients were randomly assigned (1:1:1) to receive a single-dose of inactivated influenza vaccine followed by placebo (single-dose group, n=266), a double-dose of the vaccine followed by placebo (double-dose group, n=265), or 2 single-dose administrations of the vaccine (2-single-dose group, n=269) — the second dose was given 1 month after the first injection. Patients and researchers were masked to group allocation.

Researchers tested immune responses on plasma samples collected from patients at enrollment before the first injection, at 1 month after each injection, and within 7 days of birth from both the women and their infants. The primary outcome was the seroconversion rate to each of the vaccine strains in patients 1 month after completion of the dosing schedule. The primary safety outcomes were the frequency of local and systemic reactions after each vaccine dose.

Results revealed that seroconversion rates in patients at 1 month after the final dose were significantly higher in the double-dose group (n=230; ranging from 29% to 65% for the 3 vaccine strains) than in the single-dose group (n=230; ranging from 18% to 49%; P ≤.019 for the 3 strains). However, seroconversion rates were similar between the 2-single-doses group (n=220; ranging from 23% to 52%) and the single-dose group (P ≥.20 for the 3 strains). Among the infants born to mothers who received the double-dose vaccine, results demonstrated a higher hemagglutination-inhibition antibody geometric mean titers, compared with infants of mothers who received the single-dose vaccine. However, there was no significant difference between these infants, or their mothers, in terms of those who achieved titers >1/40.

Safety outcomes were similar among the 3 groups, except for a higher incidence of local injection-site reactions among women in the double-dose group.

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This study had several limitations. First, the differential use of antiretroviral therapy in some patients during pregnancy may have influenced antibody responses to the vaccine. In addition, only one influenza season was covered, and only a single inactivated vaccine formulation was assessed at a single study site. Also, a low proportion of patients had CD4 counts of less than 350 cells per μL, which may have prevented researchers from generalizing findings to a population with severe immunosuppression. Further, only 76% of the infants were included in the analysis of haemagglutination-inhibition antibody titers on or before the age of 7 days. Lastly, the observed immunogenicity in the single-dose group was lower than expected in the sample size calculation, which may have affected the power of the study.

The study researchers concluded that administering a second dose of inactivated influenza vaccine or doubling the dose of antigen does not increase the immunogenicity of the vaccine in pregnant women with HIV compared with pregnant women without HIV and that more immunogenic vaccines may be needed for pregnant women with HIV to effectively transfer vaccine-induced antibodies to their infants.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Nunes MC, Cutland CL, Moultrie A, et al., for the Maternal Flu Trial Team. Immunogenicity and safety of different dosing schedules of trivalent inactivated influenza vaccine in pregnant women with HIV: a randomised controlled trial [published online January 3, 2020]. Lancet HIV. doi: 10.1016/S2352-3018(19)30322-4