Partial Protection againstPlasmodium vivaxBlood-Stage Infection inSaimiriMonkeys by Immunization with a Recombinant C-Terminal Fragment of Merozoite Surface Protein 1 in Block Copolymer Adjuvant

Abstract

Merozoite surface protein 1 is a candidate for blood-stage vaccines against malaria parasites. We report here an immunization study ofSaimiri monkeys with a yeast-expressed recombinant protein containing the C terminus of Plasmodium vivax merozoite surface protein 1 and two T-helper epitopes of tetanus toxin (yP2P30Pv20019), formulated in aluminum hydroxide (alum) and block copolymer P1005. Monkeys immunized three times with yP2P30Pv20019 in block copolymer P1005 had significantly higher prechallenge titers of immunoglobulin G (IgG) antibodies against the immunogen and asexual blood-stage parasites than those immunized with yP2P30Pv20019 in alum, antigen alone, or phosphate-buffered saline (PBS) (P < 0.05). Their peripheral blood mononuclear cell proliferative responses to immunogen stimulation 4 weeks after the second immunization were also significantly higher than those from the PBS control group (P < 0.05). Upon challenge with 100,000 asexual blood-stage parasites 5 weeks after the last immunization, monkeys immunized with yP2P30Pv20019 in block copolymer P1005 had prepatent periods longer than those for the control alone group (P > 0.05). Three of the five animals in this group also had low parasitemia (peak parasitemia, ≤20 parasites/μl of blood). Partially protected monkeys had significantly higher levels of prechallenge antibodies against the immunogen than those unprotected (P < 0.05). There was also a positive correlation between the prepatent period and titers of IgG antibodies against the immunogen and asexual blood-stage parasites and a negative correlation between accumulated parasitemia and titers of IgG antibodies against the immunogen (P < 0.05). These results indicate that when combined with block copolymer and potent T-helper epitopes, the yeast-expressed P2P30Pv20019 recombinant protein may offer some protection against malaria.

Immune responses elicited by co‐immunization of Plasmodium vivax and P. falciparum MSP‐1 using prime‐boost immunization strategies

“…In addition, several studies on naturally acquired immunity showed that the antibodies (IgG1 and IgG3) against this antigen are correlated with protection (20)(21)(22)(23). Moreover, among residents of West African countries, the presence of anti-PfMSP-1 19 -specific antibodies correlated with resistance to the disease (20,22) and purified MSP-1 19 -specific IgG from human sera inhibited erythrocytic invasion in vitro (24).…”

“…Therefore, numerous studies have been conducted to evaluate the efficacy of the merozoite surface protein-1 (MSP-1) (3-10) as one of the most important blood-stage vaccine candidates that is present on the surface of all known Plasmodium spp., including P. vivax (PvMSP-1) and P. falciparum (PfMSP-1). Antibody to the C-terminal region of this protein (MSP-1 19 ) has been shown to block parasite invasion in vitro (11)(12)(13). Earlier studies have demonstrated that immune responses elicited separately by PvMSP-1 19 (14,15) or PfMSP-1 19 (16)(17)(18) antigens in mice induced high levels of IgG1 antibodies followed by IgG2a and IgG2b as well as a high level of IFN-c. A partial protection was also observed after immunization of nonhuman primates with PfMSP-1 19 (5) and PvMSP-1 19 (19).…”

“…Antibody to the C-terminal region of this protein (MSP-1 19 ) has been shown to block parasite invasion in vitro (11)(12)(13). Earlier studies have demonstrated that immune responses elicited separately by PvMSP-1 19 (14,15) or PfMSP-1 19 (16)(17)(18) antigens in mice induced high levels of IgG1 antibodies followed by IgG2a and IgG2b as well as a high level of IFN-c. A partial protection was also observed after immunization of nonhuman primates with PfMSP-1 19 (5) and PvMSP-1 19 (19). In addition, several studies on naturally acquired immunity showed that the antibodies (IgG1 and IgG3) against this antigen are correlated with protection (20)(21)(22)(23).…”

“…Regarding malaria vaccine development, various research groups around the world have focused on a single vaccine by selected different antigens, expression systems and primeboost strategies. However, to the best of our knowledge, no investigations of using the combination of PvMSP-1 19 + PfMSP-1 19 antigens against two human malaria species have been performed yet. Therefore, the final goal of our efforts for multicomponent vaccine research is to develop an effective and efficient multi-species vaccine that induces a long-lasting immunity against both P. vivax and P. falciparum parasites.…”

“…Therefore, the final goal of our efforts for multicomponent vaccine research is to develop an effective and efficient multi-species vaccine that induces a long-lasting immunity against both P. vivax and P. falciparum parasites. To achieve this goal, the present investigation was designed to evaluate humoral and cellular immune responses when either two recombinant antigens (rPvMSP-1 19 + rPfMSP-1 19 ) or two plasmid constructs (pcDNA3.1 hygro-PvMSP-1 19 + pcDNA3.1 hygro-PfMSP-1 19 ) were administered in combination at a single site in mice by using different immunization strategies (protein ⁄ protein, DNA ⁄ DNA and DNA ⁄ protein).…”