Chimeric alphavirus vaccine candidates for chikungunya.
Chikungunya virus (CHIKV) is an emerging alphavirus that has caused major epidemics in India and islands off the east coast of Africa since 2005. Importations into Europe and the Americas, including one that led to epidemic transmission in Italy during 2007, underscore the risk of endemic establishment elsewhere. Because there is no licensed human vaccine, and an attenuated Investigational New Drug product developed by the U.S. Army causes mild arthritis in some vaccinees, we developed chimeric alphavirus vaccine candidates using either Venezuelan equine encephalitis attenuated vaccine strain TC-83, a naturally attenuated strain of eastern equine encephalitis virus (EEEV), or Sindbis virus as a backbone and the structural protein genes of CHIKV. All vaccine candidates replicated efficiently in cell cultures, and were highly attenuated in mice. All of the chimeras also produced robust neutralizing antibody responses, although the TC-83 and EEEV backbones appeared to offer greater immunogenicity. Vaccinated mice were fully protected against disease and viremia after CHIKV challenge.
Wang
Eryu
E
Center for Biodefense and Emerging Infectious Diseases, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, United States.
Volkova
Eugenia
E
Adams
A Paige
AP
Forrester
Naomi
N
Xiao
Shu-Yuan
SY
Frolov
Ilya
I
Weaver
Scott C
SC
D000330:Aedes; D018354:Alphavirus Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D002646:Chikungunya virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004663:Encephalitis Virus, Eastern Equine / Q000276:immunology; D005814:Genes, Viral; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000235:genetics; D012845:Sindbis Virus / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014709:Vero Cells; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D015678:Viral Structural Proteins; D014765:Viral Vaccines