Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes: Comparison of their immunogenicity and capacity to induce protective immunity

Mauricio Rodrigues, Shengqiang Li, Kenichiro Murata, Dolores Rodriguez, Juan Ramon Rodriguez, Igor Bacik, Jack R. Bennink, Jonathan W. Yewdell, Adolfo Garcia-Sastre, Ruth S. Nussenzweig, Mariano Esteban, Peter Palese, Fidel Zavala

Research output: Contribution to journalArticlepeer-review

Abstract

We compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. The CD8+ T cell epitope of the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. These recombinant viruses were found to be equally efficient at inducing CS-specific CD8+ T cells in mice. A third recombinant virus, which expresses a B cell epitope of the CS protein, induced neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the CD8+ T cell epitope and of the B cell epitope did not impair the capacity of this recombinant virus to induce malaria-specific CD8+ T cells and neutralizing Abs. The immunogenicity of a vaccinia virus, expressing the entire CS protein, was compared with that of a highly attenuated vaccinia strain expressing the same protein and with that of another vaccinia virus expressing only the CD8+ T cell epitope. All three vaccinia virus recombinants elicited CS-specific CD8+ cells and a potent inhibitory response against pre-erythrocytic stages of malaria parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage development, and protection against malaria infection resulted from repeatedly immunizing the animals with recombinant influenza viruses followed by boosters with a recombinant vaccinia virus. These findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates.

Original languageEnglish (US)
Pages (from-to)4636-4648
Number of pages13
JournalJournal of Immunology
Volume153
Issue number10
StatePublished - Nov 15 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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