Latent cytomegalovirus is associated with reduced functional antibody induction following Plasmodium falciparum infection

Latent cytomegalovirus (CMV) infection has widely reported immunomodulatory effects on the immune system, leading to altered responses to vaccination or infection with other pathogens. However, the impact of CMV on the immune response to the malaria parasite Plasmodium falciparum is unknown. Here we assessed antibody and cellular responses in malaria-naive volunteers during Controlled Human Malaria Infection (CHMI) with blood stage P. falciparum parasites. Latent CMV infection was associated with reduced induction of parasite specific IgG, IgG1, and functional antibodies following infection. Within the T-follicular helper (Tfh) cell compartment, CMV was associated with a skew towards Tfh1 cell subsets before and after malaria, and reduced activation of Tfh2 cells which have been previously associated with antibody induction during malaria. Taken together, CMV latent infection impacts the phenotype of Tfh cells required for robust antibody induction to malaria and may have particular importance in malaria endemic countries where CMV infection is almost universal and acquired early in life.