Cell-Mediated and humoral immune responses to trivalent inactivated influenza vaccine in high-risk groups

Abstract

Introduction: Pregnancy is associated with physiological and immunological changes that leave women vulnerable to influenza infection and associated complications. This evolutionary adaptation is not fully understood, but evidence indicates a shift from cell-mediated immunity toward humoral immunity, which places pregnant women at a heightened risk to severe influenza illness, exacerbated further by co-infection with HIV. Tuberculosis (TB) is a major health issue resulting in ill-health among millions of people every year, with approximately one third of the population having latent TB. The considerable gains achieved in reducing the incidence of TB have reversed in recent years due to the emergence of HIV. Currently little data exist on the effectiveness of influenza vaccination in individuals co-infected with HIV and TB. We evaluate and compare the cellular and humoral immune responses to the trivalent inactivated influenza vaccine in these high-risk groups. Methods: In 2013 we conducted (1) a double-blind randomised controlled trial, involving HIV-infected pregnant women, (2) two prospective, open labelled trials involving HIV-infected non-pregnant women, and HIV-uninfected pregnant and non-pregnant women, respectively, as well as in 2014 (3) a prospective, open labelled four arm trial involving HIV/TB co-infected, HIV-infected TB-uninfected, HIV-uninfected TB-infected and HIV-uninfected TB-uninfected adults. Cell-mediated, as measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay, and humoral, as measured by hemagglutination inhibition (HAI) assay, immune responses to the seasonal iii trivalent inactivated influenza vaccine were evaluated and compared between respective study groups at baseline and approximately 1 month post-vaccination. Results: in this study we report no significant differences in cell-mediated immune (CMI) responses among HIV-infected pregnant and non-pregnant women at both pre-vaccination and post-vaccination. Vaccination improved CMI responses to all three influenza strains, with the only significant increases observed for A/H1N1 in HIV-infected pregnant and non-pregnant women and B/Yamagata in HIV-infected non-pregnant women. Following stratification of women into low- (LB) and high-baseline (HB) responses we found significantly improved cellular immune responses to the influenza viruses in the LB groups for both HIV-infected and HIV-uninfected pregnant and non-pregnant women, whereas HB women tended to exhibit a declined immune response. We show significantly enhanced humoral immune responses to the influenza vaccination in TB-infected and TB-uninfected adults living with HIV post-vaccination, with little significant differences between the two groups. We found a similar trend in HIV-uninfected adults infected with and without TB; however HIV-uninfected adults achieved higher geometric mean titers than adults living with HIV. Conclusion: among the HIV-infected pregnant and non-pregnant women, it appears pregnancy did not play as significant a role in attenuating CMI responses to vaccination as HIV infection. However, a significantly higher percentage of HIV-infected pregnant women were on antiretroviral therapy (ART) at the time of enrolment which may have influenced the role of CD4+ T-cell count on CMI responses and could possibly explain the iv similar responses observed in these two study groups. Cellular immune responses to vaccination were significantly greater in HIV-uninfected non-pregnant women compared to HIV-uninfected pregnant women, adding further evidence to the detrimental impact pregnancy has on CMI responses. Pre-existing immunity to influenza vaccination plays a major role on CMI responses following vaccination. Women with high-baseline responses tended to display decreased responses whereas women with low-baseline responses showed significantly improved responses. We propose that a potential threshold may exist where the quantity of memory T-cells reaches maximal levels in the blood system. We also show that vaccination with trivalent inactivated influenza vaccine (IIV3) was relatively immunogenic in HIV-infected TB-infected/uninfected adults, albeit not the magnitude observed in healthy populations. However, in adults living without HIV-infection, we showed that influenza vaccination was significantly immunogenic in both adults infected with TB and those without. Additionally, we show that infection with TB does not appear to affect humoral immune responses, even in the HIV-infected population.