Adjuvants and MHCII modulate the immunogenicity of subdominant epitopes in Plasmodium vivax Duffy binding protein

TL;DR

The study shows how adjuvants and vaccine design can shift immune responses to less dominant regions of a malaria protein, which could help in developing better vaccines.

Contribution

The study reveals how adjuvants and epitope mutations can overcome subdominance in Plasmodium vivax Duffy binding protein.

Findings

Adjuvants GLA-SE or alum enhance responses to subdominant epitopes when immunodominant regions are mutated.

MHCII haplotype can restrict the immunogenicity of subdominant epitopes.

Boosting is necessary to generate strong antibody responses to subdominant epitopes.

Abstract

Antibody responses to protein antigens are driven by epitope hierarchies that promote the immunogenicity of select epitopes. For antigenically variable pathogens, immune responses toward conserved epitopes are critical to elicit strain-transcending antibodies, yet these epitopes are often subdominant. Designing vaccines that focus immune responses to these epitopes requires an understanding of which components can overcome subdominance. Using the Plasmodium vivax Duffy binding protein with a defined subdominant region, we investigated how immunization strategies affect the immunogenicity of this region. We demonstrated that antigens with mutations in immunodominant epitopes, combined with the adjuvants GLA-SE or alum, overcame the subdominance of this region. However, these effects were largely negated by MHCII restriction. Further, robust antibody responses toward subdominant epitopes depend on boosting, which alters the epitope hierarchy and enables the recruitment of germinal center B cells specific to the subdominant epitopes. Our study provides valuable insights for designing subunit vaccines targeting subdominant epitopes.

•Adjuvants modulate antibody responses toward a subdominant region in PvDBPII•Mutations in immunodominant epitopes further enhanced epitope-specific responses•MHCII haplotype can restrict the immunogenicity of subdominant epitopes•Boosting is required to achieve potent immunogenicity toward subdominant epitopes

Adjuvants modulate antibody responses toward a subdominant region in PvDBPII

Mutations in immunodominant epitopes further enhanced epitope-specific responses

MHCII haplotype can restrict the immunogenicity of subdominant epitopes

Boosting is required to achieve potent immunogenicity toward subdominant epitopes

Vaccinology; Immunology; Parasitology

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