Detection of febrile responses in venezuelan equine encephalitis virus (VEEV) infected mice

Author:

Martin, SS, Parker, MD, Bakken, R, Price, JL, Lind, CL, Hart, MK, Fine, DL

Summary:

Abstract. This abstract presented at the December 9, 2008 poster session of the American Society of Tropical Medicine and Hygiene meeting discusses encephalitic virus infections in infected mice.

V3526, a live attenuated vaccine for VEEV subtype IA/B, induces mild fevers in nonhuman primates (NHP) and humans following vaccination. It is unknown if mice, the traditional model for encephalitic virus infections, develop a fever following vaccination with V3526. To date the murine response to V3526 and other VEEV vaccines has been limited to clinical observations (ruffled fur, hunched back, etc.) and generation of antibodies. The recent development of telemetric implants for small animals has made more sensitive assessment of murine responses to VEEV and vaccines a possibility. This study was designed to monitor body temperatures and activity in mice following administration of VEE IA/B TrD and V3526, and to evaluate the utility of telemetry as a diagnostic indicator of disease in nonclinical VEEV studies. Three groups of BALB/c mice were implanted with telemeters (Data Sciences International) and baseline data were collected for 7 days. Mice in each group were inoculated subcutaneously with either 1x104 pfu of VEE IA/B TrD, 1x104 pfu of V3526 or control material. Temperature and activity data were collected on each mouse for 28 days post-inoculation or until death. Blood samples were collected prior to and at 28 days postinoculation for monitoring VEEV neutralizing antibody responses. All mice in the VEE IA/B TrD group presented the classical clinical symptoms associated with infection and exhibited fevers 1.5ºC above normal within 4.5 days post-inoculation. Temperatures then decreased and remained subnormal until death. Temperatures in mice inoculated with V3526 or control material were not significantly elevated above baseline at any time throughout the study. From these studies we conclude: 1) telemetry is a sufficiently sensitive tool for detecting fevers in mice challenged with virulent VEEV and 2) V3526 does not induce a febrile response in mice as seen in NHP and humans. Studies in progress will utilize telemetry to assess adverse effects in mice and NHP that receive various inactivated VEEV vaccine/adjuvant formulations.