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

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.

• Authors: M Rodrigues, S Li, K Murata, D Rodriguez, J R Rodriguez, I Bacik, J R Bennink, J W Yewdell, A Garcia-Sastre, R S Nussenzweig
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 153 Issue 10 Pg. 4636-48 (Nov 15 1994) ISSN: 0022-1767 [Print] United States
• PMID: 7525709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Protozoan
• Epitopes
• Protozoan Proteins
• Recombinant Proteins
• circumsporozoite protein, Protozoan

Topics

• Amino Acid Sequence
• Animals
• Antigens, Protozoan (genetics, immunology)
• B-Lymphocytes (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cytotoxicity, Immunologic
• Enzyme-Linked Immunosorbent Assay (methods)
• Epitopes (immunology)
• Female
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• Orthomyxoviridae (genetics)
• Plasmodium yoelii (immunology)
• Protozoan Proteins (immunology)
• Recombinant Proteins (immunology)
• Vaccinia virus (genetics)