Vectored vaccines to protect against PRRSV

Abstract

PRRSV is the causative agent of the most important infectious disease affecting swine herds worldwide, producing great economic losses. Commercially available vaccines are only partially effective in protection against PRRSV. Moreover, modified live vaccines may allow virus shedding, and could revert generating virulent phenotypes. Therefore, new efficient vaccines are required. Vaccines based on recombinant virus genomes (virus vectored vaccines) against PRRSV could represent a safe alternative for the generation of modified live vaccines. In this paper, current vectored vaccines to protect against PRRSV are revised, including those based on pseudorabies virus, poxvirus, adenovirus, and virus replicons. Special attention has been provided to the use of transmissible gastroenteritis virus (TGEV) as vector for the expression of PRRSV antigens. This vector has the capability of expressing high levels of heterologous genes, is a potent interferon-α inducer, and presents antigens in mucosal surfaces, eliciting both secretory and systemic immunity. A TGEV derived vector (rTGEV) was generated, expressing PRRSV wild type or modified GP5 and M proteins, described as the main inducers of neutralizing antibodies and cellular immune response, respectively. Protection experiments showed that vaccinated animals developed a faster and stronger humoral immune response than the non-vaccinated ones. Partial protection in challenged animals was observed, as vaccinated pigs showed decreased lung damage when compared with the non-vaccinated ones. Nevertheless, the level of neutralizing antibodies was low, what may explain the limited protection observed. Several strategies are proposed to improve current rTGEV vectors expressing PRRSV antigens.

N-Linked Glycosylation of GP5 of Porcine Reproductive and Respiratory Syndrome Virus Is Critically Important for Virus Replication In Vivo

“…The amino acids in the proximal region of the ectodomain are highly variable (17). Potential N-linked glycosylation sites have been positioned at N30, N33, N34, and N35 in the hypervariable region upstream of the neutralization epitopes in genotype 2 PRRSV isolates (6,17). In the present study, the substitutions of the glycosylation site N in the hypervariable region were revealed in some field viruses (Fig.…”

“…The substitution for N44 by S, K, T, and D was found in about 2% of genotype 2 viruses (17). The N51 glycosylation site was considered highly conserved, as about 0.2% of the sequenced GP5 lacked the N-glycosylation site (6,17). Some viruses lost specific glycosylation sites but propagated well in MARC-145 cells or PAMs (17), which implied that the existence of GP5-associated glycans per se was not vital to the life cycle of the virus.…”

Porcine reproductive and respiratory syndrome virus vaccines: Immunogenicity, efficacy and safety aspects

“…These efforts reportedly included use of several adjuvants [40][41][42] , use of mixed strains of PRRSV [43,44] , and generation of alternative vaccines, i.e. DNA vaccine [45,46] , subunit vaccine [47,48] , synthetic peptide vaccine [13] , viral vector vaccines using adenovirus [49][50][51] , PRV [52,53] , poxvirus [54,55] , and transmissible gastroenteritis virus [56] as vectors, alphavirusderived replicon [57] , bacterial vector vaccine [58] , insect cellderived vaccine [59] , and plant-derived vaccine [60,61] (Table 4). These efforts, however, can achieve at best some, but not all, properties of an ideal PRRS vaccine.…”

Expression of the nucleocapsid protein of Porcine Reproductive and Respiratory Syndrome Virus in soybean seed yields an immunogenic antigenic protein

“…Antibodies continue to be a valuable indicator of exposure, but the role of neutralizing antibodies in protection against PRRS is controversial. Recent efforts to produce recombinant proteins of GP5 and M, encoded by ORFs 5 and 6, respectively, in a vectored vaccine resulted in faster and stronger humoral immune response in vaccinated than in non-vaccinated pigs (Cruza et al 2010). The transmissible gastroenteritis virus (TGEV) derived vector (rTGEV) expressing GP5 and M, known as main inducers of neutralizing antibodies and cellular immune response, respectively, afforded only partial protection against PRRSV challenged animals as the level of neutralizing antibodies was low.…”