Porcine reproductive and respiratory syndrome virus (PRRSV) is widespread in many swine-producing countries, causing substantial economic losses to the swine industry. Porcine alveolar macrophage (PAM) is considered the primary target for PRRSV replication in pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or gene fragments, insertion of foreign genes, and swapping genes between PRRSV strains or between PRRSV and other members of the Arteriviridae family. In this review, we describe the approaches to construct an infectious cDNA for PRRSV and the ten major applications of these infectious clones to study virus biology and virus–host interaction, and to design a new generation of vaccines with improved levels of safety and efficacy.

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, and Bacillus Calmette-Guérin (BCG) remains the only clinically approved vaccine. An enduring challenge in TB vaccine development is systematic antigen selection from a large repertoire of potential candidates. We performed an efficacy screen in mice of antigens that are targets of CD4 T cells in humans. We found striking heterogeneity in protective efficacy, and most of the top protective antigens are not currently in clinical development. We observed immunologic cross-reactivity among phylogenetically clustered antigens, reflecting common CD4 epitopes. We developed a trivalent mRNA vaccine consisting of PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), which augmented and exceeded BCG protection in multiple mouse models. Finally, we observed cellular immune responses to these antigens in 84% of humans exposed to M. tuberculosis. These data advance our understanding of TB vaccine immunology and define a vaccine concept for clinical development.

Virus neutralization profiles against primary infection sera and corresponding antigenic cartography are integral part of the COVID-19 and influenza vaccine strain selection processes. Human single variant exposure sera have previously defined the antigenic relationships among SARS-CoV-2 variants but are now largely unavailable due to widespread population immunity. Therefore, antigenic characterization of future SARS-CoV-2 variants will require an animal model, analogous to using ferrets for influenza virus. We evaluated neutralization profiles against 23 SARS-CoV-2 variants in nonhuman primates (NHPs) after single variant exposure and generated an NHP-derived antigenic map. We identified a distant antigenic region occupied by BA.2.86, JN.1, and the descendants KP.2, KP.3, and KZ.1.1.1. We also found that the monovalent XBB.1.5 mRNA vaccine induced broad immunity against the mapped antigenic space. In addition, substantial concordance was observed between our NHP-derived and two human antigenic maps, demonstrating the utility of NHPs as a surrogate for antigenic cartography in humans.

The Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows for frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as nanocarriers for delivering DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. The intramuscular administration of a single dose of the LNP-DNA vaccines resulted in robust systemic and mucosal responses in pigs. Importantly, the vaccinated pigs were fully protected against challenge infection with the homologous IAV-S strain, with only 1 out of 12 vaccinated pigs shedding a low amount of viral genomic RNA in its nasal cavity. No gross or microscopic lesions were observed in the lungs of the vaccinated pigs at necropsy. Thus, the LNP-DNA vaccines are highly effective in protecting pigs against the homologous IAV-S strain and can serve as a promising platform for the rapid development of IAV-S vaccines.

African swine fever virus (ASFV) is the causative agent of a lethal disease in pigs. Highly virulent strains of ASFV are known to suppress the induction of type I interferons (IFNs), while naturally attenuated strains do not exhibit this capability. Thus, the ability to suppress IFN is assumed to be associated with viral virulence. ASFV genome encodes many proteins capable of disrupting crucial components of host immune response pathways. Notably, these viral proteins interfere with the induction of type I IFNs by targeting various steps of the cGAS-STING signaling pathway. Additionally, certain viral proteins impede the expression of interferon-stimulated genes by interfering with the JAK-STAT pathway. Consequently, ASFV proteins hamper both IFN production and the induction of antiviral responses by IFNs. This review article summarizes the viral proteins responsible for suppressing various steps of the cGAS-STING and JAK-STAT signaling pathways and discusses the potential application of this knowledge to the rational design of a live-attenuated ASFV vaccine.