Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults

Abstract

Introduction: The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy.

Methods: A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity.

Results: 297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 = 31-58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related.

Conclusion: Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population.

Trial registration: ClinicalTrials.gov NCT00764998.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Proportion of patients with doubling of HAI titres.

The proportion of vaccine recipients with doubling of HAI titres are described at week 4 (i.e. 4 weeks following the initial vaccination), week 8 (i.e. 8 weeks following the initial vaccination and 4 weeks following the booster dose in groups 1 and 2), and week 20. The HAI titre response is described for each of the three antigens included in the administered vaccine (A/H3N2/Uruguay, A/H1N1/Brisbane, B/Florida). Group 1 (single dose followed by single dose booster at week 4), Group 2 (double dose followed by double dose booster at week 4) and Group 3 (single dose without booster at week 4) are depicted.

Figure 2. Proportion of patients achieving seroconversion (quadrupling of HAI titres).

The proportion of vaccine recipients with a quadrupling of HAI titres are described at week 4 (i.e. 4 weeks following the initial vaccination), week 8 (i.e. 8 weeks following the initial vaccination and 4 weeks following the booster dose in groups 1 and 2), and week 20. The HAI titre response is described for each of the three antigens included in the administered vaccine (A/H3N2/Uruguay, A/H1N1/Brisbane, B/Florida). Group 1 (single dose followed by single dose booster at week 4), Group 2 (double dose followed by double dose booster at week 4) and Group 3 (single dose without booster at week 4) are depicted.

Figure 3. Patients with baseline HAI titres ≤ 10: proportion achieving seroprotection (titres ≥40).

The proportion of vaccine recipients with baseline HAI titres ≤10 achieving seroprotection (titres ≥40) are described at week 4 (i.e. 4 weeks following the initial vaccination), week 8 (i.e. 8 weeks following the initial vaccination and 4 weeks following the booster dose in groups 1 and 2), and week 20. The HAI titre response is described for each of the three antigens included in the administered vaccine (A/H3N2/Uruguay, A/H1N1/Brisbane, B/Florida). Group 1 (single dose followed by single dose booster at week 4), Group 2 (double dose followed by double dose booster at week 4) and Group 3 (single dose without booster at week 4) are depicted.

Figure 4. HAI titre doubling over time as a function of baseline HIV RNA suppression.

The proportion of vaccine recipients achieving HAI doubling at week 4, 8 and 20 is described as a function of whether HIV RNA was below the lower limit of detection at baseline (