title: Immune Responses to Circulating and Vaccine Viral Strains in HIV-Infected and Uninfected Children and Youth Who Received the 2013/2014 Quadrivalent Live-Attenuated Influenza Vaccine.
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.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Curtis
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Mariangeli Freitas
authors.initials: MF
authors.lastname: Ning
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: David Jeremy
authors.initials: DJ
authors.lastname: Claypool
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Jalbert
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Patterson
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Frank
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Colorado Denver , Aurora, CO , USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Ir
authors.affiliation: Children's Hospital of Colorado , Aurora, CO , USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Armon
keywords: ELISPOT; HIV infection; LAIV; cell-mediated immunity; children; influenza vaccine; neutralization