Helminth infection modulates the immunogenicity of COVID-19 vaccines in mice without compromising protective efficacy

Objectives Helminth parasites infect over a quarter of the global population and can profoundly modulate host immunity, potentially influencing vaccine performance and the spread of pandemic pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the high global endemicity of helminth infections, their impact on immune responses to various COVID-19 vaccines remains unknown. This study aimed to evaluate the impact of Schistosoma infection on the immunogenicity and protective efficacy of messenger RNA (mRNA)- and protein-based COVID-19 vaccines. Methods Mice with Schistosoma infection and non-infected controls were immunized with either an mRNA-based COVID-19 vaccine or an alum-adjuvanted spike protein vaccine. Vaccine-induced humoral and cellular immune responses were assessed, and protective efficacy was evaluated using a SARS-CoV-2 challenge model. Results COVID-19 mRNA vaccination induced strong spike-specific antibody and CD4 T-cell responses in Schistosoma -infected mice comparable to non-infected controls, despite a Th2/regulatory-biased immune environment, although multifunctional CD8 T-cell responses were reduced. Alum-adjuvanted protein vaccination elicited robust humoral but weaker cellular immunity, with comparable immune responses in infected and non-infected mice. Following SARS-CoV-2 challenge, both vaccine platforms conferred effective protection, with substantial viral clearance and minimal lung pathology. Conclusions mRNA and protein vaccines elicit distinct immune profiles; however, both protect effectively against SARS-CoV-2 infection in mice with concurrent helminth infection.