Probing the attenuation and protective efficacy of a candidate chikungunya virus vaccine in mice with compromised interferon (IFN) signaling

Vaccine. 2011 Apr 5;29(16):3067-73. doi: 10.1016/j.vaccine.2011.01.076. Epub 2011 Feb 5.


Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes explosive outbreaks of febrile illness associated with rash, and painful arthralgia. The CHIK vaccine strain 181/clone25 (181/25) developed by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) was shown to be well-tolerated and highly immunogenic in phase I and II clinical trials although it induced transient arthralgia in some healthy adult volunteers. In an attempt to better understand the host factors that are involved in the attenuating phenotype of CHIK 181/25 vaccine virus we conducted studies in interferon (IFN)-compromised mice and also evaluated its immunogenic potential and protective capacity. Infection of AG129 mice (defective in IFN-α/β and IFN-γ receptor signaling) with CHIK 181/25 resulted in rapid mortality within 3-4 days. In contrast, all infected A129 mice (defective in IFN-α/β receptor signaling) survived with temporary morbidity characterized by ruffled appearance and body weight loss. A129 heterozygote mice that retain partial IFN-α/β receptor signaling activity remained healthy. Infection of A129 mice with CHIK 181/25 induced significant levels of IFN-γ and IL-12 while the inflammatory cytokines, TNFα and IL-6 remained low. A single administration of the CHIK 181/25 vaccine provided both short-term and long-term protection (38 days and 247 days post-prime, respectively) against challenge with wt CHIKV-La Reunion (CHIKV-LR). This protection was at least partially mediated by antibodies since passively transferred immune serum protected both A129 and AG129 mice from wt CHIKV-LR and 181/25 virus challenge. Overall, these data highlight the importance of IFNs in controlling CHIK 181/25 vaccine and demonstrate the ability of this vaccine to elicit neutralizing antibody responses that confer short-and long-term protection against wt CHIKV-LR challenge.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alphavirus Infections / immunology
  • Alphavirus Infections / prevention & control*
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Chikungunya virus / immunology*
  • Cytokines / immunology
  • Gene Deletion
  • Interferons / immunology*
  • Mice
  • Mice, Inbred A
  • Mice, Knockout
  • Neutralization Tests
  • Receptor, Interferon alpha-beta / genetics
  • Receptors, Interferon / genetics
  • Vaccines, Attenuated / immunology
  • Viral Vaccines / immunology*
  • Viremia / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Receptors, Interferon
  • Vaccines, Attenuated
  • Viral Vaccines
  • interferon gamma receptor
  • Receptor, Interferon alpha-beta
  • Interferons