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<jats:title>ABSTRACT</jats:title> <jats:p>Although merozoite surface protein 1 (MSP-1) is a leading candidate vaccine antigen for blood-stage malaria, its efficacy in clinical trials has been limited in part by antigenic polymorphism and potentially by the inability of protein-in-adjuvant vaccines to induce strong cellular immunity. Here we report the design of novel vectored <jats:italic>Plasmodium falciparum</jats:italic> vaccines capable of overcoming such limitations. We optimized an antigenic insert comprising the four conserved blocks of MSP-1 fused to tandemly arranged sequences that represent both allelic forms of the dimorphic 42-kDa C-terminal region. Inserts were expressed by adenoviral and poxviral vectors and employed in heterologous prime-boost regimens. Simian adenoviral vectors were used in an effort to circumvent preexisting immunity to human adenoviruses. In preclinical studies these vaccines induced potent cellular immune responses and high-titer antibodies directed against MSP-1. The antibodies induced were found to have growth-inhibitory activity against dimorphic allelic families of <jats:italic>P. falciparum</jats:italic>. These vectored vaccines should allow assessment in humans of the safety and efficacy of inducing strong cellular as well as cross-strain humoral immunity to <jats:italic>P. falciparum</jats:italic> MSP-1.</jats:p>

Original publication

DOI

10.1128/iai.00315-10

Type

Journal

Infection and Immunity

Publisher

American Society for Microbiology

Publication Date

11/2010

Volume

78

Pages

4601 - 4612