Vaccination with virosomally formulated recombinant CyRPA elicits protective antibodies against Plasmodium falciparum parasites in preclinical in vitro and in vivo models

Abstract

The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine. This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells. The aim of the present study was to develop a humancompatible formulation of the PfCyRPA vaccine candidate and confirming its activity in preclinical studies. Recombinant PfCyRPA expressed in HEK 293 cells was chemically coupled to phosphoethanolamine and then incorporated into the membrane of unadjuvanted influenza virosomes approved as antigen delivery system for humans. Laboratory animals were immunised with the virosome-based PfCyRPA vaccine to determine its immunogenic properties and in particular, its capacity to elicit parasite binding and growth-inhibitory antibodies. The vaccine elicited in mice and rabbits high titers of PfCyRPA-specific antibodies that bound to the blood-stage parasites. At a concentration of 10 mg/mL, purified total serum IgG from immunised rabbits inhibited parasite growth in vitro by about 80%. Furthermore, in a P. falciparum infection mouse model, passive transfer of 10 mg of purified total IgG from PfCyRPA vaccinated rabbits reduced the in vivo parasite load by 77%. Influenza virosomes thus represent a suitable antigen delivery system for the induction of protective antibodies against the recombinant PfCyRPA, designating it as a highly suitable component for inclusion into a multivalent and multi-stage virosomal malaria vaccine.npj Vaccines (2020) 5:9 ; https://doi.

The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target

“…In a NOD-scid IL2Ry null mouse (NSG) model grafted with human erythrocytes, there was a marked decrease (90%) in parasitaemia after P. falciparum challenge when pretreated with 2.5 mg of monoclonal antibody SB1.6 or C12 (Table 2) [65]. A follow-up study showed that rabbit immunization with PfCyRPA integrated into influenza virosomes elicits neutralizing antibodies that slow parasite growth in the NSG mouse model [66].…”

Nanovaccines against Animal Pathogens: The Latest Findings

“…This formulation seems to be a suitable antigen delivery system inducing strong growth-inhibitory Abs in vivo and in vitro. The system and the candidate antigen can be further adapted as a multivalent and multi-stage virosomal anti-malarial vaccine [ 181 ].…”

Sistemas de expresión de proteínas recombinantes para el análisis funcional de antígenos de Plasmodium falciparum y Plasmodium vivax: una revisión

“…Con este sistema se identificaron potenciales candidatos a vacuna evaluando la eficacia protectora de anticuerpos contra múltiples combinaciones de antígenos de P. vivax (65) y regiones clave de unión del parásito a las células diana. Además, se identificó la interacción entre una proteína de P. falciparum homóloga a retoculocitos-5 (RH-5) y su receptor de la superficie celular de los eritrocitos Basigina (66), que resulta ser clave en el proceso de invasión a eritrocitos (67, 68) y ha permitido el desarrollo de la vacuna en etapa eritrocítica de PfRH-5 (23), PfEBA (69), PfCyRPA (20,70).…”