AUTHOR=Kyei-Baafour Eric , Kusi Kwadwo Asamoah , Arthur Fareed K.N. , Tiendrebeogo Regis W. , Owusu-Yeboa Eunice , Singh Susheel K. , Friedrich Sarah , Gerds Thomas A. , Dodoo Daniel , Theisen Michael , Adu Bright TITLE=High opsonic phagocytosis activity and growth inhibition of merozoites are associated with RON4 antibody levels and protect against febrile malaria in Ghanaian children JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1161301 DOI=10.3389/fimmu.2023.1161301 ISSN=1664-3224 ABSTRACT=Background

Naturally acquired immunity to malaria may involve different immune mechanisms working in concert, however, their respective contributions and potential antigenic targets have not been clearly established. Here, we assessed the roles of opsonic phagocytosis and antibody-mediated merozoite growth inhibition in Plasmodium falciparum (P. falciparum) infection outcomes in Ghanaian children.

Methods

The levels of merozoite opsonic phagocytosis, growth inhibition activities and six P. falciparum antigen-specific IgG of plasma samples from children (n=238, aged 0.5 to 13 years) were measured at baseline prior to the malaria seasons in southern Ghana. The children were then actively and passively followed up for febrile malaria and asymptomatic P. falciparum infection detection in a 50-week longitudinal cohort. P. falciparum infection outcome was modelled as a function of the measured immune parameters while accounting for important demographic factors.

Results

High plasma activity of opsonic phagocytosis [adjusted odds ratio (aOR)= 0.16; 95%CI= 0.05 - 0.50, p = 0.002], and growth inhibition (aOR=0.15; 95% CI = 0.04-0.47; p = 0.001) were individually associated with protection against febrile malaria. There was no evidence of correlation (b= 0.13; 95% CI= -0.04-0.30; p=0.14) between the two assays. IgG antibodies against MSPDBL1 correlated with opsonic phagocytosis (OP) while IgG against PfRh2a correlated with growth inhibition. Notably, IgG antibodies against RON4 correlated with both assays.

Conclusion

Opsonic phagocytosis and growth inhibition are protective immune mechanisms against malaria that may be acting independently to confer overall protection. Vaccines incorporating RON4 may benefit from both immune mechanisms.