Semliki forest virus and Kunjin virus RNA replicons elicit comparable cellular immunity but distinct humoral immunity.
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 beta-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.
Tannis
Laura Lee
LL
Center for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, MDCL-5025, 1200 Main Street West, Hamilton, Ont., Canada L8N 3Z5.
Gauthier
Andree
A
Evelegh
Carole
C
Parsons
Robin
R
Nyholt
Dana
D
Khromykh
Alexander
A
Bramson
Jonathan L
JL
D018354:Alphavirus Infections / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D005822:Genetic Vectors; D007111:Immunity, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000008:administration & dosage / Q000276:immunology*; D012093:Replicon / Q000276:immunology*; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
D012367:RNA, Viral