Combining antimalarial drugs and vaccine for malaria elimination campaigns: a randomized safety and immunogenicity trial of RTS,S/AS01 administered with dihydroartemisinin, piperaquine, and primaquine in healthy Thai adult volunteers

Abstract

Introduction: RTS,S/AS01 is currently the most advanced malaria vaccine but provides incomplete, short-term protection. It was developed for use within the expanded program on immunizations (EPI) for African children. Another use could be adding mass RTS,S/AS01 vaccination to the integrated malaria elimination strategy in the Greater Mekong Subregion (GMS), where multidrug-resistant P.falciparum strains have emerged and spread. Prior to evaluating RTS,S/AS01 in large-scale trials we assessed whether the vaccine, administered with and without antimalarial drugs, is safe and immunogenic in Asian populations.Methods: An open-label, randomized, controlled phase 2 trial was conducted in healthy, adult Thai volunteers. Seven vaccine regimens with and without antimalarial drugs (dihydroartemisinin-piperaquine plus a single low dose primaquine) were assessed. Antibody titres against the PfCSP full-length (NANP) 6, PfCSP anti-C-term, PfCSP full-length (N + C-Terminal) were measured by standard enzyme-linked immunosorbent assays. Liquid chromatography was used to measure piperaquine, primaquine and carboxyprimaquine concentrations. Results: 193 volunteers were enrolled and 186 study participants completed the 6 months follow-up period. One month after the last vaccination all study participants had seroconverted to the PfCSP (NANP)6, and the PfCSP Full Length (N + C-Terminal). More than 90% had seroconverted to the Pfanti-C-Term CSP. There was no indication that drug concentrations were influenced by vaccine regimens or the antibody levels by the drug regimens. Adverse events were similarly distributed between the seven treatment groups. No serious adverse events attributable to the study interventions were detected. Conclusion: This study found that RTS,S/AS01 with and without dihydroartemisinin-piperaquine plus a single low dose primaquine was safe and immunogenic in a healthy, adult Asian population. ARTICLE HISTORY

Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease

“…Vaccine-linked chemotherapy has been proposed as an improved treatment strategy for parasitic diseases to both reduce infection and reduce morbidity ( Bergquist et al., 2005 ; von Seidlein et al., 2020 ). We were the first to demonstrate in mouse models of acute infection that vaccine-linked chemotherapy using a low dose of benznidazole and a low dose of vaccine, consisting of a stable squalene emulsion containing recombinant Tc24-C4 protein and a TLR4 agonist adjuvant, either E6020 or glucopyranosyl lipid A (GLA), which leads to greater reductions in parasite burdens, cardiac inflammation, and cardiac fibrosis when compared to BNZ or vaccine only treatment ( Jones et al., 2018 ; Cruz-Chan et al., 2021 ).…”

Artemisinin resistance and malaria elimination: Where are we now?

“…Interestingly, the vaccine showed more protective effect in children living in lower transmission settings than in higher transmission settings (RTS,S Clinical Trials Partnership, 2015). A recent study in healthy adult Thai volunteers demonstrated that the RTS,S/AS01 vaccine was safe and immunogenic in this population and not affected by the concomitant administration of DP and primaquine, which are antimalarials commonly used in MDA (von Seidlein et al, 2020). These data support the use of ACTs in combination with malaria vaccine RTS,S/AS01 in MDA to accelerate P. falciparum elimination in Asia.…”

Recent Progress on the Versatility of Virus-Like Particles

“…These proteins can spontaneously enter the cells to form VLPs that subsequently serve as a vaccine [96]. In phase 3 clinical trials, this vaccine has been shown to reduce (~50%) the incidence of severe malaria in children between the ages of 5 and 17 months, with good safety and efficacy [69]. The vaccine can also induce moderate levels of CD4+ T cells and antibodies against CSP, a secreted protein of the sporozoite stage of the parasite [97].…”