The long range goal of our research is to develop an effective vaccine against human immunodeficiency virus type-1 (HIV-1) infection. We plan to use avian paramyxoviruses (APMVs) as vectors for delivery of HIV-1 proteins. APMVs do not cause disease in humans and there is no preexisting immunity in humans to APMVs. There are nine serotypes of APMVs, therefore, several serologically distinct vectors can be developed to express different HIV genes for use in prime-boost immunization approach. As a first step towards our goal, we propose here studies to optimize the expression level of HIV-1 envelope glycoprotein (Env), its incorporation into virus particles and the strategy of immunization. We have chosen to use APMV-1, also known as Newcastle disease virus (NDV), because this is the most studied member among APMVs. The results obtained with NDV can be extended to other APMV serotypes in the future. The first objective of our proposal is to identify the optimal 5'and 3'untranslated regions of NDV genes for insertion into HIV Env transcriptional unit to enhance its expression. We will also attempt to enhance the incorporation of HIV Env into NDV envelope by replacement of transmembrane domain and cytoplasmic tail sequences of HIV Env protein with those of NDV F protein individually and collectively. The second objective of our proposal is to evaluate different inoculation routes and prime-boost approaches for eliciting robust systemic and mucosal immune responses in guinea pigs. The optimal strategies will subsequently be moved into monkey studies.
HIV is a major global health problem. Currently effective vaccines against HIV are not available. Although treatment with antiviral drugs can decrease the progression of the disease, antiviral drugs are not practical due to high cost and appearance of drug resistant mutant viruses. Therefore, the goal of our research is to develop an effective vaccine against HIV using NDV as a vaccine vector.
|Khattar, Sunil K; DeVico, Anthony L; LaBranche, Celia C et al. (2016) Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins. J Virol 90:1682-6|
|Khattar, Sunil K; Manoharan, Vinoth; Bhattarai, Bikash et al. (2015) Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges. MBio 6:e01005|
|Khattar, Sunil K; Palaniyandi, Senthilkumar; Samal, Sweety et al. (2015) Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus. Hum Vaccin Immunother 11:504-15|
|Nayak, Baibaswata; Nayak, Shreeraj; Paldurai, Anandan et al. (2013) Evaluation of the genetic diversity of avian paramyxovirus type 4. Virus Res 171:103-10|
|Khattar, Sunil K; Samal, Sweety; LaBranche, Celia C et al. (2013) Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector. PLoS One 8:e78521|