Impact of aging and HIV infection on serologic response to seasonal influenza vaccination

Abstract

Objective: To determine influence of age and HIV infection on influenza vaccine responses.

Design: Evaluate serologic response to seasonal trivalent influenza vaccine (TIV) as the immunologic outcome in HIV-infected (HIV⁺) and age-matched HIV negative (HIV⁻) adults.

Methods: During 2013-2016, 151 virologically controlled HIV⁺ individuals on antiretroviral therapy and 164 HIV⁻ volunteers grouped by age as young (<40 years), middle aged (40-59 years) and old (≥60 years) were administered TIV and investigated for serum antibody response to vaccine antigens.

Results: At prevaccination (T0) titers were in seroprotective range in more than 90% of participants. Antibody titers increased in all participants postvaccination but frequency of classified vaccine responders to individual or all three vaccine antigens at 3-4 weeks was higher in HIV⁻ than HIV⁺ adults with the greatest differences manifesting in the young age group. Of the three vaccine strains in TIV, antibody responses at T2 were weakest against H3N2 with those to H1N1 and B antigens dominating. Among the age groups, the titers for H1N1 and B were lowest in old age, with evidence of an age-associated interaction in HIV⁺ persons with antibody to B antigen.

Conclusion: Greater frequencies of vaccine nonresponders are seen in HIV⁺ young compared with HIV⁻ adults and the observed age-associated interaction for B antigen in HIV⁺ persons are supportive of the concept of premature immune senescence in controlled HIV infection. High-potency influenza vaccination recommended for healthy aging could be considered for HIV⁺ adults of all ages.

Fig. 1.. Antibody responses to individual vaccine antigens between study groups.

Antibody titers for H1N1, H3N2 and B were determined before (T0), and day 7 (T1), day 21–28 (T2) and months 5–7 (T3) after vaccination by hemagglutination inhibition assay in HIV⁻ (dotted lines) and HIV⁺ (solid lines) in young (red), middle aged (green) and old (blue) individuals. Geometric mean titers are shown for each time point. Line graphs depict antibody response to (a); H1N1, (b); B and (c); H3N2 at T0, T1, T2 and T3. P values were calculated with Student’s t test. Each symbol for the statistics represents the comparison between indicated groups with a P less than 0.05. Tables S1 and S2,http://links.lww.com/QAD/B231 provide additional information related to all comparisons including actual P values.

Fig. 2.. Vaccine responses in HIV⁻ and HIV⁺ groups.

Bar graphs indicate the vaccine responders and nonresponders for individual vaccine antigens and participants who met criteria for absolute or other (response only to one or two antigens) categories in (a–d); full cohort (flu responses of people in relation to age and HIV) in (a); total participants, (b); young, (c); middle aged and (d); old and (e and f); finding novel determinants of flu responses cohort with baseline titer or less 320 in (e); total participants, (f); young, (g); middle aged and (h); old. Analyzed by chi-squared test. *P < 0.01; **P < 0.001; ***P < 0.0001. ^#Significant difference compared with Y⁻ and O⁻; ^¶significant compared with Y⁺ and O⁺.

Fig. 3.. Spider plots showing contribution of antibody response to individual antigens to whole vaccine antibody response.

Linear regression analysis performed using different age groups of HIV⁺ and HIV⁻ at each time point. Product measure from standardized coefficient and Pearson correlation coefficient were calculated to identify the proportion of each antigens contributing to whole vaccine response at T0, T1, T2 and T3, (a–d) Statistical significance of the data is depicted in Supplementary Tables S3 and S4, http://links.lww.com/QAD/B231.

Fig. 4.. Correlation of HIV and age with response to H1N1 and B antigens.

Log₂ hemagglutination inhibition responses to H1N1 and B were correlated with age in both HIV⁺ and HIV⁻ by Pearson correlation. Interaction between age and HIV infection on antibody response was tested by univariate multiple linear regression analysis. Significant inverse correlation is evident between age and antibody response to H1N1 at (a) T0, (b) T1, (c) T2, and B at (d) T1, (e) T2, (f) T3, (g) fold change B response at T3. HIV and age interaction for (f), B titer at T3 and (g), fold change B titer at T3. Filled circles indicate HIV⁺ and open circles indicate HIV⁻. Red regression line indicates HIV⁺ and green line for HIV⁻. (h–k) HIV infection affects the B response starting at the age range of 36–45 years: HIV⁺ and HIV⁻ groups were divided into eight age groups and mean log₂ B titer at each time point was compared between HIV⁺ and HIV⁻. Log B titer for HIV⁺ (solid line) and HIV⁻ (dotted line) at (h) T0, (i), T1, (j), T2 and (k), T3. At each time point, a linear model is fitted to the B titer for each age group. Star indicates the P value of less than 0.05 between HIV⁺ and HIV⁻. *P < 0.01; **P < 0.001; ***P < 0.0001.