Efficience of human Plasmodium falciparum malaria vaccine candidates in Aotus lemurinus monkeys

Abstract

The protective efficacy of several recombinant and a synthetic Plasmodium falciparum protein was assessed in Aotus monkeys. The rp41 aldolase, the 190L fragment of the MSA-1 protein and fusion 190L-CS. T3 protein containing the CS.T3 helper "universal" epitope were emulsified in Freund's adjuvants and injected 3 times in groups of 4-5 monkeys each one. The synthetic polymer Spf (66)30 also emulsified in Freund's adjuvants was injected 6 times. Control groups for both experiments were immunized with saline solution in the same adjuvant following the same schedules. Serology for malaria specific antibodies showed seroconversion in monkeys immunized with the recombinant proteins but not in those immunized with the polymer nor in the controls. Challenge was performed with the 10(5) parasites from the P. falciparum FVO isolate. Neither rp41 nor Spf(66)30 induced protection, whereas 190L induced significant delay of parasitemia. The fusion of the CS.T3 epitope to 190L significantly increased its protective capacity.

Sterile protection againstPlasmodium vivaxmalaria by repeated blood stage infection in a non-human primate model

“…Previous trials of P. falciparum and P. vivax vaccine candidates have demonstrated the utility of the Aotus model in supporting vaccine development [44][45][46]. Various asexual stage vaccine candidate antigens have been subjected to testing in Aotus [45,[47][48][49][50][51][52][53][54][55], but only a few have shown some level of efficacy in human clinical trials [15,56]. Development of highly effective strain-transcendent immunity against malaria is a universal goal of vaccine developers [57].…”

Aotus Lemurinus Griseimembra Monkeys: A Suitable Model for Plasmodium Vivax Sporozoite Infection

“…[3][4][5][6][7][8][9] As a result, these monkey species have been used successfully for preclinical assessment of malaria vaccine candidates targeting parasite blood stages, [10][11][12] as well as for the assessment of new antimalarial lead compounds. 3,13,14 However, infection by sporozoites has generally been more difficult to achieve.…”

Direcionando as proteínas MSP-119 de Plasmodium vivax e Plasmodium yoelii para células dendríticas in vivo: análise das respostas imunes celular humoral.

“…No caso específico do Brasil, há relatos de que a infecção pelo P. vivax possa causar formas graves e letais da doença, sendo que os principais problemas estão relacionados com alterações hematológicas, ruptura esplênica, disfunções renais e pulmonares(64).Os mecanismos de proteção durante a fase eritrocítica do desenvolvimento incluem a inibição da invasão das hemácias por anticorpos capazes de neutralizar proteínas da superfície do merozoíto e de estimular a fagocitose de eritrócitos infectados. parcial contra desafio infeccioso em primatas(88). A partir desses resultados foi desenvolvida uma vacina multivalente chamada de "combinação B" capaz de induzir proteção parcial em ensaios clínicos, sendo a subunidade 190L o componente mais imunogênico(89).…”