Semliki Forest virus and Kunjin virus RNA replicons elicit comparable cellular immunity but distinct humoral immunity

• Published in: Vaccine Vol. 23; no. 33; pp. 4189 - 4194
• Main Authors: Tannis, Laura Lee, Gauthier, Andree, Evelegh, Carole, Parsons, Robin, Nyholt, Dana, Khromykh, Alexander, Bramson, Jonathan L.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 21.07.2005; Elsevier; Elsevier Limited
• Subjects: Alphavirus; Alphavirus Infections - immunology; Animals; Antibody Formation; Apoptosis; Applied microbiology; Biological and medical sciences; Cell culture; Deoxyribonucleic acid; DNA; Flavivirus; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Immune response; Immunity, Cellular; Immunization; Immunogenicity; Kunjin virus; Lymphocytes; Medical research; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Peptides; Plasmids; Replicon - immunology; RNA polymerase; RNA replicon; RNA, Viral - administration & dosage; RNA, Viral - immunology; Semliki Forest virus; Semliki forest virus - genetics; Semliki forest virus - immunology; Statistical analysis; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Cytotoxic - immunology; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; West Nile Fever - immunology; West Nile virus - genetics; West Nile virus - immunology; Alphavirus; Vaccine; RNA replicon; Flavivirus; Virus; Semliki forest virus; Kunjin virus; Togaviridae; Cellular immunity; Japanese encephalitis group virus; Flaviviridae; Humoral immunity
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.04.005

RNA replicons offer a number of qualities which make them attractive as vaccination vectors. Both alphavirus and flavivirus replicon vaccines have been investigated in preclinical models yet there has been little direct comparison of the two vector systems. To determine whether differences in the biology of the two vectors influence immunogenicity, we compared two prototypic replicon vectors based on Semliki Forest virus (SFV) (alphavirus) and Kunjin virus (KUN) (flavivirus). Both vectors when delivered as naked RNAs elicited comparable CD8+ T cell responses but the SFV vectors elicited greater humoral responses to an encoded cytoplasmic antigen β-galactosidase. Studies in MHC class II-deficient mice revealed that neither vector could overcome the dependence of CD4+ T cell help in the development of humoral and cellular responses following immunization. These studies indicate that the distinct biology of the two replicon systems may differentially impact the adaptive immune response and this may need to be considered when designing vaccination strategies.