Effect of Antihelminthic Treatment on Vaccine Immunogenicity to a Seasonal Influenza Vaccine in Primary School Children in Gabon: A Randomized Placebo-Controlled Trial

Abstract

Background: Helminth infections are a major public health problem, especially in the tropics. Infected individuals have an altered immune response with evidence that antibody response to vaccination is impaired. Hence, treatment of helminth infections before vaccination may be a simple intervention to improve vaccine immunogenicity. In the present study we investigated whether a single-dose antihelminthic treatment influences antibody responses to a seasonal influenza vaccine in primary school children living in Gabon, Central Africa.

Methods: In this placebo-controlled double-blind trial conducted in Gabon the effect of a single-dose antihelminthic treatment with 400 mg albendazole versus a placebo one month prior to immunization with a seasonal influenza vaccine was investigated. Antiviral antibody titers against all three vaccine strains were assessed by haemagglutination inhibition (HI) test at baseline (Day 0; vaccination) and four weeks (Day 28) as well as 12 weeks (Day 84) following vaccination. Vaccine-specific memory B-cell response was measured at Day 0 and Day 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The trial is registered with the Pan African Clinical Trials Registry (PACTR) (PACTR201303000434188).

Results: 98 school children aged 6-10 years were randomly allocated to receive either antihelminthic treatment or placebo and were vaccinated one month after the treatment. The prevalence of helminths at baseline was 21%. Vaccine-specific HI titers against at least one of the three vaccine strains increased at Day 28 and Day 84 in all participants. HI titers against both influenza A strains as well as memory B-cell response were modestly higher in the antihelminthic treated group compared to the placebo group but the difference was not statistically significant. Total but not specific IgA was elevated in the antihelminthic treated group compared to the control group at Day 28.

Conclusion: In our setting antihelminthic treatment had no significant effect on influenza vaccine immunogenicity. A trend towards better antiviral and vaccine immunogenicity in the antihelminthic treated group encourages studies to be conducted with alternative treatment schedules or in populations with a higher helminth burden.

Fig 1. Study profile.

⁺Patients were excluded, because of infection with S. haematobium. *Participants not terminating the study are summarized as lost to follow up (n = 16).

Fig 2. Antibody titers against the three vaccine strains at baseline (day 0), day 28 and day 84.

Red lines indicate the mean of all volunteers of the antihelminthic treated group (AT) and blue lines indicate the mean of all participants of the placebo group. Dashed lines indicate antibody titers of each participant.

Fig 3. Differences of HI titers between the respective visits (day 28, day 84) and day 0 (baseline).

Red and blue colors represent the pre-treated (AT) and control group.

Fig 4. Total IgA at day 0, day 28 and day 84 in antihelminthic treated (AT) (red blots) and placebo group (blue blots).

Fig 5. Vaccine specific IgA at day 0, day 28 and day 84 in antihelminthic treated (AT) (red) and placebo group (blue).

Fig 6. Vaccine-specific IgG ASCs determined by B-cell ELISpot at day 0 and day 84.

Fig 7. Vaccine-specific IgG ASCs at day 0 and day 84, in antihelminthic treated (AT) and placebo group.

Red and blue represent antihelminthic treated (AT) and control group.