Abstract
Plasmodium vivax is the world’s most widely distributed human malaria parasite, with over 2.8 billion people at risk in Asia, the Americas, and Africa. The 80–90% new P. vivax malaria infections are due to relapses which suggest that a vaccine with high efficacy against relapses by prevention of hypnozoite formation could lead to a significant reduction in the prevalence of P. vivax infections. Here, we describe the development of new recombinant ChAdOx1 and MVA vectors expressing P. cynomolgi Thrombospondin Related Adhesive Protein (PcTRAP) and the circumsporozoite protein (PcCSP). Both were shown to be immunogenic in mice prior to their assessment in rhesus macaques. We confirmed good vaccine-induced humoral and cellular responses after prime-boost vaccination in rhesus macaques prior to sporozoite challenge. Results indicate that there were no significant differences between mock-control and vaccinated animals after challenge, in terms of protective efficacy measured as the time taken to 1st patency, or as number of relapses. This suggests that under the conditions tested, the vaccination with PcTRAP and PcCSP using ChAdOx1 or MVA vaccine platforms do not protect against pre-erythrocytic malaria or relapses despite good immunogenicity induced by the viral-vectored vaccines.
Highlights
Plasmodium vivax is considered to be the biggest hurdle towards malaria eradication
To assess the potency of our vaccines prior to the Nonhuman Primates (NHP) immunizations and challenge, the immunogenicity of our viral-vectored vaccines was first assessed in mice by measuring cellular response in C57Bl/6 mice which suggested that Modified Vaccinia Ankara (MVA) Plasmodium cynomolgi Circumsporozoite Protein (PcCSP) and PcTRAP vaccines immunized as prime induced low T-cell responses as described previously [23] while the ChAdOx1 vaccine counterpart demonstrated significantly higher T cell responses as previously shown by other ChAdOx1 vaccines encoding various different antigens [18]
Our results show that despite induction of humoral and cellular responses in all vaccinated group of NHPs immunized with ChAdOx1–MVA (PcCSP/PcTRAP), there was no effect in protection against P. cynomolgi sporozoite infection or relapse, as shown by the development of the parasite blood-stage in both scenarios
Summary
Plasmodium vivax is considered to be the biggest hurdle towards malaria eradication This protozoa is the most widespread malaria parasite in humans, as well as the most difficult to eliminate from endemic countries in Asia, the Americas and Africa. P. vivax as well as P. cynomolgi, have a sophisticated ability to hide in the infected host for long periods of time by developing structures in hepatocytes known as hypnozoites [3] These dormant forms change dramatically the epidemiological landscape of malaria, as reactivation by unknown mechanisms within days, months or years after the first contact with the parasite, causing a relapse and the onset of malaria symptoms in complete absence of mosquitoes [3,4]. It has been shown that relapses are responsible for 80–90% new P. vivax malaria infections [5,6], which suggests that targeting hypnozoites either by Vaccines 2020, 8, 363; doi:10.3390/vaccines8030363 www.mdpi.com/journal/vaccines
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