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.

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 (<50 copies/mL) (n = 226) or above this level (n = 72). Each of the three antigens included in the administered vaccine (A/H3N2/Uruguay, A/H1N1/Brisbane, B/Florida) is considered. 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.