Abstract
SummaryReticulocyte-binding protein homolog 5 (RH5) is a leading Plasmodium falciparum blood-stage vaccine candidate. Another possible candidate, apical membrane antigen 1 (AMA1), was not efficacious in malaria-endemic populations, likely due to pre-existing antimalarial antibodies that interfered with the activity of vaccine-induced AMA1 antibodies, as judged by in vitro growth inhibition assay (GIA). To determine how pre-existing antibodies interact with vaccine-induced RH5 antibodies, we purify total and RH5-specific immunoglobulin Gs (IgGs) from malaria-exposed Malians and malaria-naive RH5 vaccinees. Infection-induced RH5 antibody titers are much lower than those induced by vaccination, and RH5-specific IgGs show differences in the binding site between the two populations. In GIA, Malian polyclonal IgGs show additive or synergistic interactions with RH5 human monoclonal antibodies and overall additive interactions with vaccine-induced polyclonal RH5 IgGs. These results suggest that pre-existing antibodies will interact favorably with vaccine-induced RH5 antibodies, in contrast to AMA1 antibodies. This study supports RH5 vaccine trials in malaria-endemic regions.
Highlights
Malaria remains one of the biggest threats to global health, with estimates of 228 million clinical cases and 405,000 deaths in 2018.1 Existing antimalarial control measures, such as insecticide-treated nets, rapid diagnostics, and antimalarial drugs, have reduced malaria cases and deaths dramatically in the last two decades; the incidence rate was unchanged between 2014 and 2018.1 it is necessary to supplement existing control measures with new tools, such as vaccines.Reticulocyte-binding protein homolog 5 (RH5) is one of the leading blood-stage vaccine candidates for Plasmodium falciparum, which is the most lethal Plasmodium species that causes malaria in humans
Epidemiology of immunoglobulin Gs (IgGs) responses against RH5-CyRPARipr complex proteins in Mali The study cohort consisted of 500 individuals aged 1–65 living in the village of Kenieroba, Mali, an area of high malaria transmission with a rainy season from June to December.[29]
The total IgGs exhibited activity ranging from 0% to 100% inhibition in growth inhibition assay (GIA) (%GIA) at 10 mg/mL, and this functional activity correlated with the PfFVO (p < 0.001) and RH5.1 (p = 0.002) ELISA units (EUs) (Figure 2)
Summary
Malaria remains one of the biggest threats to global health, with estimates of 228 million clinical cases and 405,000 deaths in 2018.1 Existing antimalarial control measures, such as insecticide-treated nets, rapid diagnostics, and antimalarial drugs, have reduced malaria cases and deaths dramatically in the last two decades; the incidence rate was unchanged between 2014 and 2018.1 it is necessary to supplement existing control measures with new tools, such as vaccines.Reticulocyte-binding protein homolog 5 (RH5) is one of the leading blood-stage vaccine candidates for Plasmodium falciparum, which is the most lethal Plasmodium species that causes malaria in humans. In the two Aotus challenge studies, significant positive correlations were observed between in vitro GIA activity of antibodies and in vivo protective effects.[9,10] a recent phase I/IIa trial, conducted in a malaria-naive population, demonstrated reduced P. falciparum blood-stage multiplication rates following RH5.1/AS01B vaccination[19] and controlled human malaria infection (CHMI). This in vivo impact on parasite growth significantly correlated with in vitro GIA activity before the challenge.[20]
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