Immunogenicity and Tolerability after Two Doses of Non-Adjuvanted, Whole-Virion Pandemic Influenza A (H1N1) Vaccine in HIV-Infected Individuals

BACKGROUND: During the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals. METHODS AND FINDINGS: A standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1:40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1:40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1:40 or seroconverted after vaccination. The vaccine was well tolerated. CONCLUSION: The non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals

Serological response, defined by seroprotection^a, seroconversion^b, GMT^c and GMT ratio^c and seropositivity^d in HIV-positive individuals before and after first and second intramuscular vaccination with the whole-virion, Vero cell-derived, inactivated, non-adjuvanted pandemic H1N1 influenza vaccine.

<p>Serological response, defined by seroprotection^a, seroconversion^b, GMT^c and GMT ratio^c and seropositivity^d in HIV-positive individuals before and after first and second intramuscular vaccination with the whole-virion, Vero cell-derived, inactivated, non-adjuvanted pandemic H1N1 influenza vaccine.</p

Reverse cumulative distribution curves.

<p>On HAI assay (Panel A) and H1N1 virus-specific IgG serology by ELISA (Panel B) before vaccination (t₀), after the first vaccination (t₁) and after the second vaccination (t₂). Abbreviations: HAI, hemagglutination inhibition test; IgG, immunoglobulin G.</p

Comparison of three vaccination outcome parameters.

<p>1) three columns left: HAI seroprotection rate (HAI antibody titers ≥1∶40); 2) three columns center: IgG* seropositivity rate (IgG*>11 U); 3) two columns right: HAI seroconversion rate (4-fold increase in HAI antibody titers to ≥1∶40); at three time points: t₀, t₁ and t₂. Abbreviations: HAI, hemagglutination inhibition test; IgG*, pandemic H1N1-specific immunoglobulin G serology; t₀, time before vaccination; t₁, time after first vaccination; t₂, time after second vaccination.</p

Response of HIV-positive individuals to second intramuscular dose of the inactivated, non-adjuvanted, whole-virion pandemic influenza A (H1N1) vaccine detected by HAI and H1N1-specific IgG serology in 70 available blood samples.

<p>Abbreviations: HAI, hemagglutination inhibition test; IgG, immunoglobulin G;</p>a<p>median (95% confidence interval),</p>b<p>(%; 95% confidence interval).</p

Correlation of HAI antibody titer before vaccination (t₀), mean age of HIV-positive study participants, seroconversion rate (HAI), GMT ratio (HAI) and seropositivity (IgG* ELISA) after the second vaccination.

<p>Abbreviations: HAI, hemagglutination inhibition test; IgG*, pandemic H1N1-specific IgG, immunoglobulin G serology; t₀, time before vaccination; t₂, time after second vaccination; SD, standard deviation; GMT, geometric mean HAI titer.</p