Pre-vaccination Schistosoma mansoni and hookworm infections are associated with altered vaccine immune responses: a longitudinal analysis among adolescents living in helminth-endemic islands of Lake Victoria, Uganda

Abstract

Background: Variations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda.

Methods: Participants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-γ ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. S. mansoni infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and Strongyloides were determined by stool PCR. Linear mixed effects regression was used to assess associations.

Results: Among 478 adolescents, 70% were Schistosoma mansoni (Sm) infected and 23% hookworm infected at baseline. Sm was associated with lower Salmonella Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High Sm intensity was associated with lower BCG-specific interferon-γ and S. Typhi O:LPS-specific IgG.

Conclusions: We found inverse associations between Sm and responses to two live vaccines, whereas hookworm was positively associated with diphtheria-specific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects.

Keywords: Schistosoma mansoni; antibody responses; helminths; hookworm; immune responses; vaccines.

Figure 1

POPVAC A study site: The map of the study site shows Koome islands in Lake Victoria, where the study took place. These Islands are approximately 60 minutes from the nearest urban setting of Entebbe by a powered boat.

Figure 2

Praziquantel treatment, vaccine administration and response measurement time points. Figure adapted from (16). Peak timepoints were at 8 weeks post BCG and 4 weeks post yellow fever (YF- 17D), oral typhoid (Ty21a), human papilloma virus (HPV) and 24 weeks post tetanus/diphtheria (Td) vaccination. Waning timepoints were at 52 weeks post BCG and 48 weeks post YF- 17D, Ty21a, and HPV.

Figure 3

Crude associations between pre and post vaccination responses. The dots represent geometric mean ratios, and the bars 95% confidence intervals. The horizontal dashed line shows the null value of 1. IFN-g: interferon-γ; YF50: Yellow fever titres based on plaque reduction neutralizing reference tests at 50% neutralisation; YF90: Yellow fever titres based on plaque reduction neutralizing reference tests at 90% neutralisation; HPV-16: Human Papillomavirus type 16; HPV-18: Human Papillomavirus type 18.

Figure 4

Adjusted association between helminth infections and vaccine responses. Shown are geometric mean rations (dots) and 95% CI (bars). The horizontal dashed line shows the null value of 1. S. mansoni: Schistosoma mansoni; CAA, circulating anodic antigen; PCR, Polymerase Chain Reaction; IFN-g, interferon-γ; YF50, Yellow fever titres based on plaque reduction neutralizing reference tests at 50% neutralisation; YF90, Yellow fever titres based on plaque reduction neutralizing reference tests at 90% neutralisation; HPV-16, Human Papillomavirus type 16; HPV-18, Human Papillomavirus type 18.