Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs.
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 IgG₁ and IgG₂ 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.
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, USA ; Department of Veterinary Preventive Medicine, Ohio State University, Wooster, OH, USA.
Basavaraj
B
Binjawadagi
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, USA.
Varun
V
Dwivedi
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, USA ; Department of Veterinary Preventive Medicine, Ohio State University, Wooster, OH, USA.
Cordelia
C
Manickam
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, USA.
Kang
K
Ouyang
NanoScale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, Columbus, OH, USA.
Yun
Y
Wu
NanoScale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, Columbus, OH, USA.
Ly James
LJ
Lee
Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH, USA.
Jordi B
JB
Torrelles
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, USA ; Department of Veterinary Preventive Medicine, Ohio State University, Wooster, OH, USA.
Gourapura J
GJ
Renukaradhya
D000818:Animals; D056738:Cross Protection / Q000276:immunology*; D019344:Lactic Acid / Q000737:chemistry*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000517:prevention & control*; D013552:Swine; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000737:chemistry
D053769:Nanocapsules; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
cross-protection; mucosal vaccine; nanoparticles; pigs; porcine reproductive and respiratory syndrome