Reduced immunogenicity of influenza vaccines in HIV-infected compared with uninfected pregnant women is associated with regulatory T cells

Abstract

To evaluate the immunogenicity of influenza vaccines in HIV-infected pregnant women and the factors that may determine this response. Prospective, single-site study of HIV-infected and uninfected women. Pregnant women had the following immunologic measurements at vaccination, 6 weeks after immunization, and 12 weeks after delivery: hemagglutination inhibition (HAI) antibody titers, lymphocyte proliferation (LPA), interferon-γ enzyme-linked immunospot (ELISPOT), and polychromatic flow cytometric enumeration of influenza-specific effector and regulatory T cells. At vaccination, demographic and gestational characteristics did not differ significantly between the 20 HIV-infected and 18 uninfected participants. Prevaccination HAI geometric mean titers (GMTs) against all strains of influenza in the vaccines were similar between the two groups. Antibody responses to vaccination measured by GMT or four-fold titer increase were significantly lower in HIV-infected compared with uninfected pregnant women for influenza A strains. Antibody responses to influenza B were equally low in the two groups of participants. There were no significant LPA or ELISPOT responses to vaccination in either group. LPA results were significantly lower in HIV-infected compared with uninfected women at all time points, but ELISPOT were not. Influenza-specific regulatory CD4(+)FoxP3(+)% and CD4(+)IL10(+)% increased after vaccination in both groups, but significantly more in HIV-infected compared with uninfected pregnant women. Higher influenza-specific CD4(+)FoxP3(+)% postvaccination correlated with lower antibody responses to the vaccine and lower LPA results. Influenza vaccines have reduced immunogenicity in HIV-infected compared with uninfected pregnant women. In HIV-infected women, increased regulatory CD4(+)FoxP3(+)% may attenuate the immunogenicity of vaccines.