NYVAC-Pf7: a poxvirus-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria

Abstract

The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a multiantigen, multistage vaccine candidate for malaria, a disease that remains a serious global health problem and for which no highly effective vaccine exists. Genes encoding seven Plasmodium falciparum antigens derived from the sporozoite (circumsporozoite protein and sporozoite surface protein 2), liver (liver stage antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical membrane antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the parasite life cycle were inserted into a single NYVAC genome to generate NYVAC-Pf7. Each of the seven antigens was expressed in NYVAC-Pf7-infected culture cells, and the genotypic and phenotypic stability of the recombinant virus was demonstrated. When inoculated into rhesus monkeys, NYVAC-Pf7 was safe and well tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages of P. falciparum were elicited. Specific antibody responses against four of the P. falciparum antigens (circumsporozoite protein, sporozoite surface protein 2, merozoite surface protein 1, and 25-kDa sexual-stage antigen) were characterized. The results demonstrate that NYVAC-Pf7 is an appropriate candidate vaccine for further evaluation in human clinical trials.

The A-domain and the thrombospondin-related motif of Plasmodium falciparum TRAP are implicated in the invasion process of mosquito salivary glands

“…TRAP is currently being investigated for its ability to elicit protective immunity in a sporozoite vaccine (Gilbert et al, 1997;Schneider et al, 1998) and in a multicomponent malaria vaccine (Tine et al, 1996;Ockenhouse et al, 1998;Shi et al, 1999). Previous reports have demonstrated that antibodies and cytotoxic T cells directed against TRAP of different Plasmodium species can interfere with sporozoite infectivity of hepatocytes (Potocnjak et al, 1980;Rogers et al, 1992;Müller et al, 1993).…”

Utilizing poxviral vectored vaccines for antibody induction—Progress and prospects

“…A different MVA vector encoding CSP also failed to prime antibody responses in humans that could be boosted by a particulate CSP protein-in-adjuvant vaccine, as would be predicted from preclinical studies [93]. Similarly, a NYVAC vector encoding seven different antigens from P. falciparum showed antibody induction in rhesus macaques as well as the advantages of poxviral delivery in terms of insert capacity and genotypic stability [94], however only low level antibody induction was observed in a Phase I/IIa trial where three homologous immunizations were given to healthy adults [95]. Encouragingly, a Phase I clinical trial using an ALVAC vector recombinant for rabies glycoprotein G did show neutralizing serum antibody induction in a dose-dependent manner, although titres achieved were lower than those following immunization with the standard human diploid cell culture rabies vaccine [96].…”

Plasmodium falciparum pre-erythrocytic stage vaccine development

“…Several viral [96][97][98][99][100], bacterial [101][102][103][104] and parasite [105][106][107] vectors have been used in anti-malarial vaccine candidates; currently, many clinical trials are exploring their advantages to increase their potential and accelerate their use in vaccines [11,108].…”