Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy

Abstract

BackgroundWhile 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.MethodsUsing 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).ResultsFemales ≥ 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.ConclusionImmunization 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.

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults

“…The latter finding is consistent with a meta-analysis of 11 previous clinical trials showing higher antibody responses in postpubertal females than males. 36 The significance of the finding is unclear, however, as women did not experience improved VE compared with men in the studies included in the meta-analysis. 36 …”

“… 36 The significance of the finding is unclear, however, as women did not experience improved VE compared with men in the studies included in the meta-analysis. 36 …”

“…Cellular immunity is thought to underpin the long-lasting immunity to naturally transmitted P. falciparum malaria seen in adults immunized with PfSPZ Vaccine. 10 , 18 , 36 …”

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine

“…Sex was included as a covariate in DGE and enrichment analyses. Given there was no difference in immunogenicity or protective efficacy between male and female infants immunized with PfSPZ Vaccine (47), only female mice were used for the Py experiments. KSPZV1 clinical trial.…”

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial

“…The threshold of antibody correlating with reduced severe disease progression varies and needs to be independently determined for diverse infectious diseases, from protozoans, like Plasmodium falciparum 1,2 to viruses, like SARS-CoV-2 3,4 . Correlates of protection for antibody levels demarcating vaccine efficacy for COVID-19 hospitalization risk reduction have been represented in relation to COVID-19 convalescent plasma (CCP) equivalents [5][6][7] .…”