Immunogenicity and protection after challenge using heterologous prime-boost vaccine containing the three allelic variants of Plasmodium vivax circumsporozoite in murine model

Introduction: The worldwide burden of malaria remains a major public health problem due to a potential cause of morbidity and mortality for approximately 2.85 billion people living specially in Southeast Asia and Latin America. An effective vaccine against malaria has long been envisaged as an important addition to the available tools for malaria control. We believe that an efficient vaccine against Plasmodium vivax (P vivax) should represent the three different allelic forms of the circumsporozoite protein (CSP): VK 210, VK 247 and P.vivax-like. Methods and results: In this study, we used two hybrid recombinant proteins based on the PvCSP. Each one contains the three variant central repeat domains in tandem flanked by the conserved N- and C- terminus(FL) or only the C-terminus(CT) in the presence of Poli (I:C) adjuvant and Recombinant replication-defective human adenovirus serotype 5 (AdH5) and chimpanzee adenovirus serotype (AdC68) vectors with the sequence ad-PvCSP (containing the three repeats variants plus N-term and C-term regions in fusion) in a heterologous prime-boost protocols vaccination in Balb/c mice for analysis of protective immunity after challenge with P. berghei ANKA transgenic parasite expressing P. vivax CSP VK210 (Pb/PvVK210) and VK247 (Pb/PvVK247) sporozoites (spz). Survival curve (when animals reached 1% parasitemia must be euthanized) and immune responses were assessed and compared. When compared to animals in the control groups and vaccination regimens, all groups of vaccinated animals experienced a statistically significant delay in the mean prepatent period, that is the number of days between challenge and the detection of blood stage, however, sterile protection was not induced. Median prepatant period was 7,4 days [range 6-8] in heterologous vaccination regimens groups versus versus 3 days in control group. Animals in the control groups reached 1% parasitaemia on day 5 after infection, whereas the vaccinated mice showed no parasites in their blood at that time. Conclusion: Both vaccine formulation was able to elicit protective efficacy in Blab/c mice, showing a significant delay.