*Circumsporozoite Protein from* Plasmodium vivax *and Its Relationship to Human Malaria DOI: http://dx.doi.org/10.5772/intechopen.102529*

animals must undergo a surgery to remove the spleen in order to promote adequate parasitemia. This procedure may add significant result interpretation bias since organ removal causes immunological changes [81]. Thus, vaccine formulations against *P. vivax* malaria are based on chimeric parasites expressing parasite proteins [82]. The use of transgenic parasites of CSP-based vaccine formulations for the preerythrocytic phase of infection has allowed the analysis of functional inhibition of the exogenous CSP, expressed in replacement of the endogenous protein. Likewise, chimeric *P. berghei* parasites expressing the VK210 and VK247 were used to determine the protective efficacy of vaccine formulations consisting of viral vectors carrying *P. vivax* CSP alleles [82]. The results showed that this vaccine could induce protective and effective immune responses against P. vivax and that these findings could contribute to the development of a potential vaccine against malaria.

Another subunit vaccine against P. vivax malaria is also undergoing clinical trials. Named VMP001, this vaccine was expressed in *Escherichia coli* and encodes a chimeric CSP containing repeated sequences of the two alleles VK210 and VK247. The first Phase 1 trial with VMP001 showed that the vaccine was well tolerated and immunogenic, generating robust humoral and cellular responses to the vaccine antigen. The results did not demonstrate a protective sterilizing immunity; however, a delay to significant parasitemia was observed in more than 50% of the vaccinated individuals, compared with that seen in the control group [83].

Another study for *P. viva*x vaccine [79], which performed the expression in *Pichia pastoris* two chimeric proteins by merging the three central repeat regions of different CSP alleles (VK210, VK247, and *P. vivax*-like), after challenge with *P. berghei* ANKA transgenic parasites expressing Pb/PvVK210 or Pb/PvVK247 sporozoites. Significant time delays to parasitaemia were observed in all vaccinated mice. Thus, these formulations have potential for clinical evaluation due to their potential as protective vaccines against *P. vivax* malaria. Then, a group in Brazil describes the immunogenicity analysis of the vaccine formulations composed only by the PvCSP-AllFL chimeric and the influence of the PvAMA-1 combination [80]. The PvAMA-1 recombinant protein has also been previously described. The recombinant protein PvCSP-AllFL contains both N- and C-terminal and also the central repeats sequence of the *P. vivax* allelic variants while the central region contains six copies of the VK210 sequence (GDRA[A/D]GQPA), followed by six copies of *P. vivax*-like repeats (APGANQEGGAA) and five copies of the VK247 sequence (ANGAGNQPG). Laboratorial analyses using sporozoites from the *P. vivax* strain VK210 and bloodstage isolates demonstrated that these vaccine-elicited antibodies can recognize the native proteins. Immunization using this vaccine induced approximately a five fold decrease in parasitemia as assessed at day 5 post challenge, however, was not enough to neutralize the VK210 sporozoite infection.
