University of Nebraska-Lincoln, Lincoln, NE
University of Nebraska-Lincoln, Lincoln, NE
Nong Lam University, Ho Chi Minh City, Vietnam
HONORS AND AWARDS
2011 Widaman Trust Distinguished Graduate Assistant Award, UNL
My laboratory studies two important viruses of swine: porcine reproductive and respiratory syndrome virus (PRRSV) and influenza A virus of swine (IAV-S). The research topics that are studied in my laboratory include: (i) Host immune responses to natural infection or vaccination, (ii) Molecular characteristics of the viruses currently circulating in the swine population, and (iii) Viral proteins and/or epitopes capable of eliciting protective immunity. Collectively, results obtained from these studies will be valuable for the optimal design safe and effective vaccines against divergent viral strains circulating in the field.
PRRSV costs the US swine industry over $1 billion annually. Reducing the economic impact of PRRSV is therefore the top priority to the US swine industry. Although PRRS vaccines are commercially available, swine producers are not satisfied with the efficacy of the current PRRSV vaccines. One major limitation of the current PRRSV vaccines is that they do not provide optimal levels of heterologous protection, due to the substantial genetic variation among PRRSV strains circulating in the field. To overcome the genetic variation, we recently combined bioinformatics and reverse genetics to generate a synthetic PRRSV strain containing a consensus genome derived from a large set of wild type PRRSV sequences. The synthetic PRRSV strain possesses the same characteristics as naturally occurring PRRSV strains in regard to cell tropism and pathogenicity. Unlike naturally occurring PRRSV, the synthetic PRRSV strain induces type-I interferons instead of suppressing these cytokines. Most importantly, the PRRSV strain can confer exceptional levels of cross-protection against heterologous PRRSV strains. This synthetic PRRSV has been licensed to an animal health company for commercialization.
IAV-S is widespread and causes significant losses to the swine producers. Besides its economic impact, IAV-S also poses a great threat to public health due to its zoonotic potential. Therefore, successful control of IAV-S will not only reduce the economic impact of this viral pathogen to the swine industry but also alleviate the threat to public health. Currently, the commercial IAV-S vaccines are formulated based on multiple whole-inactivated virus (WIV) strains blended in oil-based adjuvants. Unfortunately, the efficacy of these vaccines is far from satisfactory. The biggest limitation of the current IAV-s vaccines is their sub-optimal levels of heterologous protection, mainly due to the substantial genetic diversity of IAV-S circulating in the field. In addition, the use of WIV vaccines may enhance the severity of clinical outcomes if the vaccinated pigs are exposed to antigenically mismatched IAV-S strains of the same subtype, a phenomenon known as vaccine-associated enhanced respiratory disease (VAERD). The long term goal is to develop a novel vaccine that would elicit a broad spectrum of heterologous protection without causing VAERD.
PEER-REVIEWED PUBLICATIONS (*corresponding author)
Kimpston-Burkgren K, Correas I, Osorio FA, Steffen D, Pattnaik AK, Fang Y, and Vu HL*. Contribution of porcine reproductive and respiratory syndrome virus minor glycoproteins in the induction of protective immunity. Accepted by Vaccine
Correas I, Osorio, FA, Steffen D, Pattnaik AK, and Vu HL*. Cross reactivity of immune responses to porcine reproductive and respiratory syndrome virus infection. Vaccine. 2017 Feb 1;35(5):782-788
Sun H, Pattnaik AK, Osorio FA and Vu HL*. Identification of viral genes associated with the interferon-inducing phenotype of a synthetic porcine reproductive and respiratory syndrome virus strain. Virology. 2016 (499); 313–321 PMID: 27736706
Vu HL*, Pattnaik AK, and Osorio FA. Strategies to broaden the cross-protective efficacy of vaccines against porcine reproductive and respiratory syndrome virus. Vet. Microbiol. 2016 (Invited review). PMID: 27692670
Workman AM*, Smith TP, Osorio FA, Vu HL*. Complete genome sequence of highly virulent porcine reproductive and respiratory syndrome virus variants that recently emerged in the United States. Genome Announc. 2016 Aug 4;4(4). pii: e00772-16. PMID: 27491998.
Vu HL*, Ma F, Laegreid WW, Pattnaik AK, Steffen D, Doster AR, and Osorio FA*. A synthetic porcine reproductive and respiratory syndrome virus strain confers unprecedented levels of heterologous protection. J Virol. 2015; 89(23):12070-83. PMID: 26401031.
Massilamany C, Gangaplara A, Basavalingappa RH, Rajasekaran RA, Vu HL, Riethoven JJ, Steffen D, Pattnaik AK, and Reddy J*. Mutations in the 5' NTR and the non-structural protein 3A of the coxsackievirus B3 selectively attenuate myocarditogenicity. PLoS One. 2015; 10(6):e0131052. PMID: 26098885.
Vu HL, Kwon B, de Lima M, Pattnaik AK, and Osorio FA*. Characterization of a serologic marker candidate for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus. Vaccine. 2013; 31(40):4330-7. PMID: 23892102.
Beura LK, Subramaniam S, Vu HL, Kwon B, Pattnaik AK, and Osorio FA*. Identification of amino acid residues important for anti-IFN activity of porcine reproductive and respiratory syndrome virus non-structural protein 1. Virology. 2012; 433(2):431-9. PMID: 22995188.
Vu HL, Kwon B, Yoon KJ, Laegreid WW, Pattnaik AK, and Osorio FA*. Immune evasion of porcine reproductive and respiratory syndrome virus through glycan shielding involves both glycoprotein 5 as well as glycoprotein 3. J Virol. 2011; 85(11):5555-64. PMID: 21411530. (Selected for Spotlight section of the issue).
Das PB, Vu HL, Dinh PX, Cooney JL, Kwon B, Osorio FA, and Pattnaik AK*. Glycosylation of minor envelope glycoproteins of porcine reproductive and respiratory syndrome virus in infectious virus recovery, receptor interaction, and immune response. Virology. 2011; 410(2):385-94. PMID: 21195444.
PD: Daniel Ciobanu, Animal Science Department/ UNL
Completed Research Support
A non-naturally occurring porcine reproductive and respiratory syndrome virus and methods of using.
Inventors: Vu H. L., Osorio F. A., Laegreid W., Pattnaik A. K., and Ma F.
Application # PCT/IB2015/052214. Priority filing date: 3/21/15