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Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine.

ABSTRACT: UNLABELLED:This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV-positive group had detectable but reduced functional Ab responses to both vaccine and nonvaccine influenza antigens. TIV enhanced Fc-mediated Ab responses in both HIV-positive and HIV-negative groups. A larger rise was generally observed in the HIV-positive group, such that there was no difference in functional Ab responses between the two groups after vaccination. The 2015 TIV enhanced functional influenza-specific Ab responses in both HIV-negative and HIV-positive subjects to a range of influenza HA proteins. The increase in functional Ab responses in the HIV-positive group supports recommendations to immunize this at-risk group. IMPORTANCE:Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy individuals, particularly if immunodeficient. There is therefore a need to increase our understanding of immunity to influenza in the context of underlying HIV infection. While antibodies can mediate direct virus neutralization, interactions with cellular Fc receptors may be important for anti-influenza immunity in vivo by facilitating antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent phagocytosis (ADP). The ability of seasonal influenza vaccines to induce antibody responses with potent Fc-mediated antiviral activity is currently unclear. Probing the ADCC and ADP responses to influenza vaccination has provided important new information in the quest to improve immunity to influenza.

SUBMITTER: Kristensen AB

PROVIDER: S-EPMC4886795 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine.

Kristensen Anne B AB Lay William N WN Ana-Sosa-Batiz Fernanda F Vanderven Hillary A HA Madhavi Vijaya V Laurie Karen L KL Carolan Louise L Wines Bruce D BD Hogarth Mark M Wheatley Adam K AK Kent Stephen J SJ

Journal of virology 20160527 12

<h4>Unlabelled</h4>This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 ...[more]

PMID: 27053553

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Project description:BackgroundThe conserved, immuno-subdominant influenza virus hemagglutinin (HA) stalk region is a potential universal group-specific influenza virus vaccine epitope. We analyzed antibody responses to H1 hemagglutinin stalk domain (H1/stalk) following trivalent influenza inactivated vaccine (IIV3) immunization in pregnant women, and association with protection against influenza virus illness.MethodsOne hundred forty-five human immunodeficiency virus (HIV)-uninfected pregnant women (68 IIV3 and 77 placebo recipients) and 140 pregnant women with HIV infection (72 IIV3 and 68 placebo recipients) were independently randomized in placebo-controlled efficacy trials of IIV3. Plasma samples were tested for H1/stalk immunoglobulin G (IgG) and hemagglutination inhibition (HAI) antibodies prevaccination and 1 month postvaccination. Women had weekly surveillance for influenza illness, confirmed by polymerase chain reaction.ResultsIncreases in H1/stalk IgG (and HAI) antibody levels were elicited post-IIV3, with responses being higher in HIV-uninfected women than in women living with HIV. Among HIV-uninfected vaccinees, there was no correlation (postvaccination) between H1/stalk and HAI antibody responses, whereas a strong correlation was observed in vaccinees with HIV. The H1/stalk IgG concentration was lower among women developing A/H1N1 illness (85.3 arbitrary units [AU]/mL) than those without A/H1N1 illness (219.6 AU/mL; P = .001). H1/stalk IgG concentration ≥215 AU/mL was associated with 90% lower odds (odds ratio, 0.09; P = .005) of A/H1N1 illness. Also, H1/stalk IgG was significantly lower among women with influenza B illness (93.9 AU/mL) than among their counterparts (215.5 AU/mL) (P = .04); however, no association was observed after adjusting for HAI titers.ConclusionsH1/stalk IgG concentration was associated with lower odds for A/H1N1 influenza virus illness, indicating its potential as an epitope for a universal vaccine against group 1 influenza virus.

Project description:BackgroundWe compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women.MethodsDuring 1st June- 30th September 2018, four groups of cohort participants-vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels.ResultsA total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs for influenza A(H1N1), A(H3N2), and B vaccine strains were not significantly different among all four groups (all p-values >0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values <0.05). The seroconversion rate was over 60% for any strain among the vaccinated groups, with the highest (88.8%) observed against A(H1N1) in the vaccinated pregnant group. Similarly, at least 75% of the vaccinated participants developed seroprotective antibody levels against all three strains; the highest seroprotection was found against A(H3N2) at 92.6% among vaccinated non-pregnant participants. Antibody responses (post-vaccination GMT, GMR, seroconversion, and seroprotection) were not significantly different between pregnant and non-pregnant women for all three strains of IIV3 (all p>0.05).ConclusionsThe 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.

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Dataset Information

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine.

Publications

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine.

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