AUTHOR=KC Natasha , Church L. W. Preston , Riyahi Pouria , Chakravarty Sumana , Seder Robert A. , Epstein Judith E. , Lyke Kirsten E. , Mordmüller Benjamin , Kremsner Peter G. , Sissoko Mahamadou S. , Healy Sara , Duffy Patrick E. , Jongo Said A. , Nchama Vicente Urbano Nsue Ndong , Abdulla Salim , Mpina Maxmillian , Sirima Sodiomon B. , Laurens Matthew B. , Steinhardt Laura C. , Oneko Martina , Li MingLin , Murshedkar Tooba , Billingsley Peter F. , Sim B. Kim Lee , Richie Thomas L. , Hoffman Stephen L. TITLE=Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1006716 DOI=10.3389/fimmu.2022.1006716 ISSN=1664-3224 ABSTRACT=Background

While prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination.

Methods

Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa).

Results

Females ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females.

Conclusion

Immunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver.