Plasmodium falciparum: Immunization with MSP1-42 induced non-inhibitory antibodies that have no blocking activities but enhanced the potency of inhibitory anti-MSP1-42 antibodies

Nagata, Mark; Wong, Teri Ann S.; Clements, David E.; Hui, George

doi:10.1016/j.exppara.2006.10.005

Cited by 1 publication

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References 41 publications

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“…To test for the presence of blocking antibodies that interfere with anti-MSP1 growth inhibitory antibodies, synchronized parasite cultures were incubated in a mixture of 20% heat inactivated anti-Construct 33-C sera and 15% anti-MSP1-42 inhibitory sera as previously described [50] . Normal rabbit sera were similarly mixed with the inhibitory anti-MSP1-42 sera as control.…”

Section: Methodsmentioning

confidence: 99%

T Cell Epitope Regions of the P. falciparum MSP1-33 Critically Influence Immune Responses and In Vitro Efficacy of MSP1-42 Vaccines

et al. 2011

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The C-terminal 42 kDa fragments of the P. falciparum Merozoite Surface Protein 1, MSP1-42 is a leading malaria vaccine candidate. MSP1-33, the N-terminal processed fragment of MSP1-42, is rich in T cell epitopes and it is hypothesized that they enhance antibody response toward MSP1-19. Here, we gave in vivo evidence that T cell epitope regions of MSP1-33 provide functional help in inducing anti-MSP1-19 antibodies. Eleven truncated MSP1-33 segments were expressed in tandem with MSP1-19, and immunogenicity was evaluated in Swiss Webster mice and New Zealand White rabbits. Analyses of anti-MSP1-19 antibody responses revealed striking differences in these segments' helper function despite that they all possess T cell epitopes. Only a few fragments induced a generalized response (100%) in outbred mice. These were comparable to or surpassed the responses observed with the full length MSP1-42. In rabbits, only a subset of truncated antigens induced potent parasite growth inhibitory antibodies. Notably, two constructs were more efficacious than MSP1-42, with one containing only conserved T cell epitopes. Moreover, another T cell epitope region induced high titers of non-inhibitory antibodies and they interfered with the inhibitory activities of anti-MSP1-42 antibodies. In mice, this region also induced a skewed TH2 cellular response. This is the first demonstration that T cell epitope regions of MSP1-33 positively or negatively influenced antibody responses. Differential recognition of these regions by humans may play critical roles in vaccine induced and/or natural immunity to MSP1-42. This study provides the rational basis to re-engineer more efficacious MSP1-42 vaccines by selective inclusion and exclusion of MSP1-33 specific T cell epitopes.

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Section: Methodsmentioning

confidence: 99%