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Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

Hiremath J, Kang KI, Xia M, Elaish M, Binjawadagi B, Ouyang K, Dhakal S, Arcos J, Torrelles JB, Jiang X, Lee CW, Renukaradhya GJ - PLoS ONE (2016)

Bottom Line: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells.Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge.In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

View Article: PubMed Central - PubMed

Affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.

ABSTRACT
Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

No MeSH data available.


Related in: MedlinePlus

Humoral immune response in vaccinated and SwIV challenged pigs.In pre-challenge pigs, the levels of specific IgG in plasma against (A) H1N1 SwIV and (B) SwIV M2e protein at DPC 0. In post-challenge pigs at DPC 7, the levels of SwIV specific IgA and IgG antibody titers (C and D); hemagglutination inhibition (HI) titers (E and F); and virus neutralization (VN) titers (G and H) in the BAL fluid and plasma samples, respectively, are shown. Each bar represents the average titer of 6 or 7 pigs ± SEM. The data of antibody titers shown in the graph are corrected values after subtracting from the background OD values.
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pone.0151922.g003: Humoral immune response in vaccinated and SwIV challenged pigs.In pre-challenge pigs, the levels of specific IgG in plasma against (A) H1N1 SwIV and (B) SwIV M2e protein at DPC 0. In post-challenge pigs at DPC 7, the levels of SwIV specific IgA and IgG antibody titers (C and D); hemagglutination inhibition (HI) titers (E and F); and virus neutralization (VN) titers (G and H) in the BAL fluid and plasma samples, respectively, are shown. Each bar represents the average titer of 6 or 7 pigs ± SEM. The data of antibody titers shown in the graph are corrected values after subtracting from the background OD values.

Mentions: To quantify humoral immune response in the vaccinated pigs, we performed IgG antibody analysis in plasma samples collected at day pre-challenge 0 (DPC 0) using pretitrated amounts of H1N1 SwIV and SwIV M2e protein by ELISA. Our results showed very low levels of specific antibody response, and the data was not statistically significant among the vaccinated pig groups (Fig 3A and 3B). Even in post-challenge plasma and BAL fluid samples of vaccinated pigs collected at DPC 7, the virus specific IgA and IgG antibody, hemagglutination inhibition (HI) and virus neutralizing (VN) antibody titers were low and the data was not significantly different among the experimental pig groups (Fig 3C–3H). Thus, our study indicated that antibody response in NPP and NPA vaccinated pigs at pre-challenge was weak or absent, and the detected antibody response at post-challenge was induced by the challenge virus. Our results suggested the need of using additional B cell antigenic peptides or the inactivated virus entrapped in NP vaccine, and coadministering with a potent adjuvant to boost the specific antibody response in pigs.


Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

Hiremath J, Kang KI, Xia M, Elaish M, Binjawadagi B, Ouyang K, Dhakal S, Arcos J, Torrelles JB, Jiang X, Lee CW, Renukaradhya GJ - PLoS ONE (2016)

Humoral immune response in vaccinated and SwIV challenged pigs.In pre-challenge pigs, the levels of specific IgG in plasma against (A) H1N1 SwIV and (B) SwIV M2e protein at DPC 0. In post-challenge pigs at DPC 7, the levels of SwIV specific IgA and IgG antibody titers (C and D); hemagglutination inhibition (HI) titers (E and F); and virus neutralization (VN) titers (G and H) in the BAL fluid and plasma samples, respectively, are shown. Each bar represents the average titer of 6 or 7 pigs ± SEM. The data of antibody titers shown in the graph are corrected values after subtracting from the background OD values.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836704&req=5

pone.0151922.g003: Humoral immune response in vaccinated and SwIV challenged pigs.In pre-challenge pigs, the levels of specific IgG in plasma against (A) H1N1 SwIV and (B) SwIV M2e protein at DPC 0. In post-challenge pigs at DPC 7, the levels of SwIV specific IgA and IgG antibody titers (C and D); hemagglutination inhibition (HI) titers (E and F); and virus neutralization (VN) titers (G and H) in the BAL fluid and plasma samples, respectively, are shown. Each bar represents the average titer of 6 or 7 pigs ± SEM. The data of antibody titers shown in the graph are corrected values after subtracting from the background OD values.
Mentions: To quantify humoral immune response in the vaccinated pigs, we performed IgG antibody analysis in plasma samples collected at day pre-challenge 0 (DPC 0) using pretitrated amounts of H1N1 SwIV and SwIV M2e protein by ELISA. Our results showed very low levels of specific antibody response, and the data was not statistically significant among the vaccinated pig groups (Fig 3A and 3B). Even in post-challenge plasma and BAL fluid samples of vaccinated pigs collected at DPC 7, the virus specific IgA and IgG antibody, hemagglutination inhibition (HI) and virus neutralizing (VN) antibody titers were low and the data was not significantly different among the experimental pig groups (Fig 3C–3H). Thus, our study indicated that antibody response in NPP and NPA vaccinated pigs at pre-challenge was weak or absent, and the detected antibody response at post-challenge was induced by the challenge virus. Our results suggested the need of using additional B cell antigenic peptides or the inactivated virus entrapped in NP vaccine, and coadministering with a potent adjuvant to boost the specific antibody response in pigs.

Bottom Line: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells.Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge.In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

View Article: PubMed Central - PubMed

Affiliation: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, Ohio, 44691, United States of America, and Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.

ABSTRACT
Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

No MeSH data available.


Related in: MedlinePlus