Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

Abstract

Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic- co -glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1) enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig)-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2) comparable and increased levels of virus-specific IgG 1 and IgG 2 antibody subtypes and production of high levels of both T-helper (Th)-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3) suppressed immunosuppressive cytokine response; 4) increased frequency of interferon-γ + lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5) complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold reduction in viral ribonucleic acid load detected in the blood. In conclusion, intranasal delivery of adjuvanted NP-KAg vaccine formulation to growing pigs elicited a broadly cross-protective immune response, showing the potential of this innovative vaccination strategy to prevent PRRS outbreaks in pigs. A similar approach to control other respiratory diseases in food animals and humans appears to be feasible.

Mutations in a Highly Conserved Motif of nsp1β Protein Attenuate the Innate Immune Suppression Function of Porcine Reproductive and Respiratory Syndrome Virus

“…In fact, we performed both a virus-neutralizing antibody assay and an ELISA using serum samples, but the results showed no significant differ-ence among pig groups infected with the WT virus and the three nsp1␤ mutants (data not shown). It is a well-established phenomenon that a strong Th1 response suppresses the Th2 response (humoral response) and vice versa, which was demonstrated previously in mice (65,66) and pigs (33,64,67). Therefore, our data suggest that the lack of an improved virus-neutralizing antibody response in nsp1␤ mutant-infected pigs could be partially caused by the strong Th1 response.…”

“…This not only was observed in serum of mutant-infected pigs but also was indicated by the increased activation of CTLs/␥␦ T cells, T helper/memory cells, and NK cells. Previously, an increased frequency of activated T helper/memory cells in pigs was shown to be beneficial in the clearance of Aujeszky's disease virus, African swine fever virus, classical swine fever virus, and PRRSV infections (33,41,(61)(62)(63)(64). Taken together, besides the induction of higher-level innate immune responses, these mutants may also have a stronger ability to augment Th1 cell-mediated adaptive immunity than the WT virus.…”

Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions

“…But like earlier results in PEDV infected experimental piglets [ 16 ], we observed significantly increased population of PEDV specific ASCs and IgA and IgG positive B cells in the ileum and spleen of sows in in vitro cultured MNCs for 6 days in the absence of viral antigen restimulation, indicating the presence of virus specific effector B cells for up to 6 months in PEDV infected sows. In one of our previous study in pigs vaccinated/infected with porcine reproductive and respiratory syndrome virus a similar recall lymphocyte response in lung MNCs and PBMC cultured in vitro in the absence of the virus antigen was observed [ 12 , 29 ].…”

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation

“…PLGA NP-entrapped bovine parainfluenza type 3 virus inoculated intranasally once elicited enhanced antibody response in mice [71] . A hallmark of PLGA NP-mediated vaccine delivery is its ability to induce enhanced and balanced Th1 and Th2 immune responses, essential for complete clearance of intracellular pathogens [72] , [73] , [74] . Therefore, to reinforce the efficiency of PLGA NPs mucosal vaccines, it is required to target the vaccine to mucosal M cells and DCs with the help of M cell targeting molecules, such as Ulex europaeus Agglutinin-I (UEA), specific immunoglobulins, and TLR ligands [44] , [75] , [76] .…”

“…In a similarly vaccinated and homologous virus challenged pigs, viremia was cleared early with augmented antibody and cytokine responses [214] . To further improve the efficacy of NanoPRRS, the vaccine was co-administered with a potent adjuvant ( M. tuberculosis whole cell lysate, M. tb WCL) that we identified earlier [205] , [215] , and observed complete clearance of detectable infectious challenged heterologous PRRSV (genetically 15% different) from the lungs [73] , [74] . Immunologically, increased VN titers (4 log2) and IFN-γ + lymphocytes were observed [74] , [213] .…”