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. 2018 Mar 14;36(12):1637-1642.
doi: 10.1016/j.vaccine.2018.01.069. Epub 2018 Feb 10.

RTS,S malaria vaccine efficacy and immunogenicity during Plasmodium falciparum challenge is associated with HLA genotype

C M Nielsen  1 , J Vekemans  2 , M Lievens  2 , K E Kester  3 , J A Regules  4 , C F Ockenhouse  5
Affiliations

RTS,S malaria vaccine efficacy and immunogenicity during Plasmodium falciparum challenge is associated with HLA genotype

C M Nielsen et al. Vaccine. .

Abstract

Although RTS,S remains the most advanced malaria vaccine, the factors influencing differences in vaccine immunogenicity or efficacy between individuals or populations are still poorly characterised. The analyses of genetic determinants of immunogenicity have previously been restricted by relatively small sample sizes from individual trials. Here we combine data from six Phase II RTS,S trials and evaluate the relationship between HLA allele groups and RTS,S-mediated protection in controlled human malaria infections (CHMI), using multivariate logistic or linear regression. We observed significant associations between three allele groups (HLA-A∗01, HLA-B∗08, and HLA-DRB1∗15/∗16) and protection, while another three allele groups (HLA-A∗03, HLA-B∗53, and HLA-DRB1∗07) were significantly associated with lack of protection. It is noteworthy that these 'protective' allele groups are thought to be at a lower prevalence in sub-Saharan African populations than in the UK or USA where these Phase II trials occurred. Taken together, the analyses presented here give an indication that HLA genotype may influence RTS,S-mediated protective efficacy against malaria infection.

Keywords: Antibody; HLA; Malaria; Protection; RTS,S.

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Figures

Fig. 1
Fig. 1
Allele groups significantly associated with protection in controlled human malaria infection (CHMI) are not associated with delays to parasitemia. The percentage of vaccinees who are protected in CHMI following vaccination (i.e. have not been diagnosed with malaria) is plotted against days since malaria challenge, comparing donors positive or negative for HLA-A*01 (A), HLA-A*03 (B), HLA-B*08 (C), HLA-B*53 (D), HLA-DRB1*15/*16 (E), and HLA-DRB1*07 (F) allele groups. The number of donors positive or negative for each allele group (n) out of a possible 222 subjects is given in the figure legends.
See this image and copyright information in PMC

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