Vaccines for Venezuelan equine encephalitis

Abstract

Arboviruses are capable of causing encephalitis in animals and human population when transmitted by the vector or potentially via infectious aerosol. Recent re-emergence of Venezuelan equine encephalitis virus (VEEV) in South America emphasizes the importance of this pathogen to public health and veterinary medicine. Despite its importance no antivirals or vaccines against VEEV are currently available in the USA. Here we review some of the older and newer approaches aimed at generating a safe and immunogenic vaccine as well as most recent data about the mechanistic of protection in animal models of infection.

Figures

Figure 1

Genomic organization of Venezuelan equine encephalitis virus.

Figure 2

Mutant strain of TC-83 with the subgenomic promoter inactivated and the translation of the structural protein genes placed under the contol of an encephalomyelocarditis virus internal ribosome entry site (IRES). From reference [58].

Figure 3

Genetic organization of chimeric Sindbis/Venezuelan equine encephalitis virus vaccine candidates described in references [21, 66]. The cis-acting sequences were derived from Sindbis virus strain Toto1101 or AR339, along with the nonstructural protein genes, while the structural protein genes were derived from Venezuelan equine encephalitis virus strain TC-83 or ZPC738. Bold letters represent SINV-specific sequence, and underlined letters represent VEEV-specific sequence. Lowercase letters indicate mutations introduced into the VEEV sequence to make the junction more SINV-like and to preserve the putative secondary structure of the 5’ UTR in the VEEV subgenomic RNA.

Figure 4

Genetic organization of alphavirus replicons and helpers used to package them into virus-like particles. In some cases, the helper construct is divided into the capsid and E2/E1 protein to minimize the change of RNA recombination that can produce complete genomes and live virus.