Abstract
The live-attenuated influenza vaccine (LAIV) has generally been more efficacious than the inactivated vaccine in children. However, LAIV is not recommended for HIV-infected children because of insufficient data. We compared cellular, humoral, and mucosal immune responses to the 2013–2014 LAIV quadrivalent (LAIV4) in HIV-infected and uninfected children 2–25 years of age (yoa). We analyzed the responses to the vaccine H1N1 (H1N1-09), to the circulating H1N1 (H1N1-14), which had significant mutations compared to H1N1-09 and to B Yamagata (BY), which had the highest effectiveness in 2013–2014. Forty-six HIV-infected and 56 uninfected participants with prior influenza immunization had blood and nasal swabs collected before and after LAIV4 for IFNγ T and IgG/IgA memory B-cell responses (ELISPOT), plasma antibodies [hemagglutination inhibition (HAI) and microneutralization (MN)], and mucosal IgA (ELISA). The HIV-infected participants had median CD4+ T cells = 645 cells/μL and plasma HIV RNA = 20 copies/mL. Eighty-four percent were on combination anti-retroviral therapy. Regardless of HIV status, significant increases in T-cell responses were observed against BY, but not against H1N1-09. H1N1-09 T-cell immunity was higher than H1N1-14 both before and after vaccination. LAIV4 significantly increased memory IgG B-cell immunity against H1N1-14 and BY in uninfected, but not in HIV-infected participants. Regardless of HIV status, H1N1-09 memory IgG B-cell immunity was higher than H1N1-14 and lower than BY. There were significant HAI titer increases after vaccination in all groups and against all viruses. However, H1N1-14 MN titers were significantly lower than H1N1-09 before and after vaccination overall and in HIV-uninfected vaccinees. Regardless of HIV status, LAIV4 increased nasal IgA concentrations against all viruses. The fold-increase in H1N1-09 IgA was lower than BY. Overall, participants <9 yoa had decreased BY-specific HAI and nasal IgA responses to LAIV4. In conclusion, HIV-infected and uninfected children and youth had comparable responses to LAIV4. H1N1-09 immune responses were lower than BY and higher than H1N1-14, suggesting that both antigenic mismatches between circulating and vaccine H1N1 and lower immunogenicity of the H1N1 vaccine strain may have contributed to the decreased H1N1 effectiveness of 2013–2014 LAIV4.
Highlights
Influenza causes seasonal disease in temperate climate areas
Age 500 cells/μl and low HIV replication on combination antiretroviral therapy (cART) mounted cellular, humoral, and mucosal responses comparable to those of uninfected controls
No differences were observed in the hemagglutination inhibition (HAI), neutralizing and mucosal IgA or in the T-cell responses to LAIV4
Summary
Influenza causes seasonal disease in temperate climate areas. It is estimated that 5–20% of the population of the US becomes infected with influenza yearly; >200,000 individuals are hospitalized with severe complications; and about 36,000 individuals die annually from influenza-related illness [1]. Seasonal influenza vaccines are the mainstay of protection against the influenza and its complications. The efficacy of the seasonal influenza vaccines depends primarily on the match between the vaccine and the circulating viruses, heterosubtypic cross-reactivity is well documented [2]. The immune status of the host and the use of liveattenuated or inactivated virus and of adjuvants contribute to the immunogenicity and efficacy of the influenza vaccines. Influenza vaccines are least immunogenic at the extremes of age and in immune compromised hosts.. The protective effect of inactivated influenza vaccines (IIV) correlates with antibody responses to the vaccines, such that a hemagglutination inhibition (HAI) antibody titer ≥40 is associated with a 50% decrease in the incidence of symptomatic disease in young adults [3]. Less is known about other age groups, but HAI titers ≥40 are used as a benchmark for licensure of influenza vaccines
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