Evaluation in Humans of a New, Inactivated Vaccine for Venezuelan Equine Encephalitis Virus (C-84)

Abstract

A new, formalin-inactivated vaccine for Venezuelan equine encephalitis (VEE) virus (C-84), prepared from an attenuated vaccine strain of virus (TC-83), was tested in humans. Only occasional, mild, local and systemic reactions were noted in 28 volunteers; no meaningful changes in clinical laboratory values occurred. The vaccine augmented preexisting titers of serum neutralizing antibody to VEE virus in seropositive recipients of TC-83 vaccine, and it induced high titers of neutralizing antibody in nonimmune subjects after one primary and two booster vaccinations. Circulating antibody persisted for at least 14 months in these persons. The neutralizing antibody produced after one dose of C-84 vaccine in immune subjects and after booster doses in nonimmune subjects had broad cross-reactivity within the VEE virus complex. The C-84 vaccine induced a VEE virus-specific lymphocyte transformation response. The vaccine was safe, and immunologic results showed it to be highly antigenic in healthy immune and nomimmune adults.

Comparison of the immunological responses and efficacy of gamma-irradiated V3526 vaccine formulations against subcutaneous and aerosol challenge with Venezuelan equine encephalitis virus subtype IAB

“…While TC-83 induces long-lasting immunity against closely related VEEV subtypes [6], major limitations of the vaccine exist including: only an approximately 80% response rate as assessed by plaque reduction neutralization test (PRNT) [7]; a 25% incidence of adverse reactions [8]; and reversion to virulence after mouse brain passages [4]. In addition, as a live virus vaccine, TC-83 cannot be used as a booster for subjects with waning antibody titers [9]. C-84 is currently used to boost antibody titers following vaccination with TC-83 and to immunize TC-83 non-responders.…”

A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

“…While TC-83 induces long-lasting immunity against closely related VEEV subtypes (Burke et al, 1977), major limitations of the vaccine exist including: an approximate 80% protection rate and 25% incidence of adverse reactions (McKinney, 1972), reversion to virulence after mouse brain passages and the ability to kill mice after intracerebral (IC) inoculation (McKinney et al, 1963). In addition to these limitations, TC-83 cannot be used as a booster for subjects with waning antibody titers (Edelman et al, 1979) which led to the development of the C-84 vaccine for boosting antibody titers or immunization of TC-83 non-responders. C-84 also has limitations in that protection was short lived thus requiring multiple boosters, and there was a lack of mucosal protection at high dosages of aerosol challenge in hamsters (Jarling and Stephenson, 1984).…”

An Inactivated Ross River Virus Vaccine Is Well Tolerated and Immunogenic in an Adult Population in a Randomized Phase 3 Trial

“…There are no other reported clinical studies of RRV vaccines. Several other inactivated whole-virus candidate vaccines against other alphaviruses such as Venezuelan equine encephalomyelitis virus, Eastern equine encephalomyelitis virus, and Western equine encephalomyelitis virus have been developed (15)(16)(17)(18)(19)(20), but none have been licensed for human use and clinical data are limited. More extensive clinical data are available for inactivated, whole-virus vaccines to prevent diseases caused by flaviviruses, which structurally resemble alphaviruses, such as tick-borne encephalitis virus (TBEV), Japanese encephalitis virus, and yellow fever virus (21)(22)(23).…”