Poly(I:C) and R848 adjuvants elicit sizeable humoral immunity to liver stage malaria antigens.

BACKGROUND AND

OBJECTIVES

Plasmodium falciparum infection remains a major global health burden due to increasing drug resistance and lack of an effective vaccine. Targeting the exoerythrocytic liver stage (LS) of malaria infection offers a promising approach to achieve sterile immunity to malaria infection. Therefore, the present work investigates the immunogenic potential of two key LS malaria antigens: circumsporozoite protein of P. falciparum (PfCSP) and liver stage-expressed tryptophan-rich protein of P. berghei (PbSLTRiP) formulated with a dual toll-like receptor (TLR) adjuvant combination, Poly(I:C) and R848, to evaluate the potency and durability of the elicited humoral response.

METHODS

BALB/c and C57BL/6 mice were immunized using a multidose regimen with PfCSP and PbSLTRiP, either alone or in combination (Poly(I:C) and R848). Humoral immune responses were quantified 30-80 days post-immunization through total IgG kinetics, functional IgG isotypes (IgG1, IgG2c/IgG2a), and antibody avidity (AI).

RESULTS

Coadministration of Poly(I:C) and R848 was shown to evoke greater antibody responses compared to antigen alone. PfCSP-specific IgG titers remained detectable up to 80 days post immunization and declined gradually over time. PbSLTRiP immunization, however, produced progressive increases in total IgG, detectable IgG2c responses, and modest changes in antibody avidity, with little non-significant difference between adjuvant regimens.

CONCLUSIONS

Combination of Poly(I:C) and R848 adjuvant induced detectable antibody responses against LS malaria antigens, with magnitudes generally like those obtained with single adjuvants. Limited statistical differences highlight preliminary trends warranting future investigations into predicted multi-epitope engagement and hypothesized B cell-mediated CD8+ T-cell cross-presentation.