Association between Protection against Clinical Malaria and Antibodies to Merozoite Surface Antigens in an Area of Hyperendemicity in Myanmar: Complementarity between Responses to Merozoite Surface Protein 3 and the 220-Kilodalton Glutamate-Rich Protein

Abstract

We performed a longitudinal clinical and parasitological follow-up study in OoDo, a village in southeast Asia in which malaria is hyperendemic, in order to assess the association between protection against malaria attacks and antibodies to three currently evaluated vaccine candidates, merozoite surface protein 1 (MSP1), MSP3, and the 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum. Our results showed that the levels of cytophilic immunoglobulin G3 (IgG3) antibodies against conserved regions of MSP3 and GLURP were significantly correlated with protection against clinical P. falciparum malaria. In contrast, the levels of noncytophilic IgG4 antibodies against GLURP increased with the number of malaria attacks. Furthermore, we observed a complementary effect of the MSP3-and GLURP-specific IgG3 antibodies in relation to malaria protection. In the individuals that did not respond to one of the antigens, a strong response to the other antigen was consistently detected and was associated with protection, suggesting that induction of antibodies against both MSP3 and GLURP could be important for the development of protective immunity. The complementarity of the responses to the two main targets of antibody-dependent cellular inhibition identified to date provides the first rational basis for combining these two antigens in a hybrid vaccine formulation.

The Impact of Immune Responses on the Asexual Erythrocytic Stages of Plasmodium and the Implication for Vaccine Development

“…Similarly, high antibody levels of MSP-1 specific IgG1 were associated with reduced morbidity (Riley et al, 1992;Al-Yaman et al, 1996) with protection against high-level parasitemia (Fowkes et al, 2010) and clinical disease (Egan et al, 1996;Cavanagh et al, 2004;Soe et al, 2004).…”

“…Evidence from field studies in Ghana (Dodoo et al, 2000), Senegal (Oeuvray et al, 2000) and East Asia (Soe et al, 2004) suggest that cytophilic antibodies are associated with a lower risk for subsequent clinical malaria episodes. These isotypes are also associated with the antibody-dependent cellular inhibition as discussed above.…”

“…Similar to MSP-1, allelic dimorphism has been reported. MSP-3 specific antibodies found in sera from malaria-endemic areas are associated with protective immunity (Soe et al, 2004). MSP-3 based vaccines have been designed as long peptides representing the conserved C-terminus of the antigen (Druilhe et al, 2005;Sirima et al, 2007).…”

Genome-Based Vaccinology Applied to Bovine Babesiosis

“…As a novel alternative to cope with this situation, multistage vaccines have been designed in an attempt to interrupt the life cycle in both vertebrate and invertebrate hosts. Using antigens from blood stages as the glutamate-rich protein (GLURP) that had been recognized as a natural antigen in acquiring immunity against malaria [82] and by the usage of sexual stage antigens Pfp48/45 that are involved in gamete fusion during sexual reproduction within the mosquito vector [83], the central objective of this alternative multiepitope vaccine is to confer immunity in the people that is at risk to acquire the infection and to reduce in long term the infection in the vector avoiding transmission [84]. The usage of more than two antigens is also an opportunity to confer immunity against parasites and to ensure the success to block the infection.…”

Synthetic Peptide Vaccines

“…These immunogens are МSP-3-LSP (Long synthetic protein) that represents the МSP-3 fragment including the residues 186-276  Bouharoun-Tayoun, 1995 and GLURP-LPS that represents the GLURP fragment including the residues 85-213 (Dodoo et al, 2000;Theisen et al, 2000Theisen et al, , 2001. These peptide immunogens were highly conservative for all plasmodium isolates; they induced formation of cytophilic antibodies of IgG1 and IgG3 subclasses; via opsonizing shizonts they attracted monocytes that caused shizont lysis (Theisen et al, 2001;Soe et al, 2004). Phase I clinical trials (Druilhe et al, 2005;Sirima et al, 2009) demonstrated formation of long (at least 1 year) immune response to these vaccines.…”