scholarly journals 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 ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Sunil K. Khattar ◽  
Vinoth Manoharan ◽  
Bikash Bhattarai ◽  
Celia C. LaBranche ◽  
David C. Montefiori ◽  
...  

ABSTRACT Newcastle disease virus (NDV) avirulent strain LaSota was used to coexpress gp160 Env and p55 Gag from a single vector to enhance both Env-specific and Gag-specific immune responses. The optimal transcription position for both Env and Gag genes in the NDV genome was determined by generating recombinant NDV (rNDV)-Env-Gag (gp160 located between the P and M genes and Gag between the HN and L genes), rNDV-Gag-Env (Gag located between the P and M genes and gp160 between the HN and L genes), rNDV-Env/Gag (gp160 followed by Gag located between the P and M genes), and rNDV-Gag/Env (Gag followed by gp160 located between the P and M genes). All the recombinant viruses replicated at levels similar to those seen with parental NDV in embryonated chicken eggs and in chicken fibroblast cells. Both gp160 and Gag proteins were expressed at high levels in cell culture, with gp160 found to be incorporated into the envelope of NDV. The Gag and Env proteins expressed by all the recombinants except rNDV-Env-Gag self-assembled into human immunodeficiency virus type 1 (HIV-1) virus-like particles (VLPs). Immunization of guinea pigs by the intranasal route with these rNDVs produced long-lasting Env- and Gag-specific humoral immune responses. The Env-specific humoral and mucosal immune responses and Gag-specific humoral immune responses were higher in rNDV-Gag/Env and rNDV-Env/Gag than in the other recombinants. rNDV-Gag/Env and rNDV-Env/Gag were also more efficient in inducing cellular as well as protective immune responses to challenge with vaccinia viruses expressing HIV-1 Env and Gag in mice. These results suggest that vaccination with a single rNDV coexpressing Env and Gag represents a promising strategy to enhance immunogenicity and protective efficacy against HIV. IMPORTANCE A safe and effective vaccine that can induce both systemic and mucosal immune responses is needed to control HIV-1. In this study, we showed that coexpression of Env and Gag proteins of HIV-1 performed using a single Newcastle disease virus (NDV) vector led to the formation of HIV-1 virus-like particles (VLPs). Immunization of guinea pigs with recombinant NDVs (rNDVs) elicited potent long-lasting systemic and mucosal immune responses to HIV. Additionally, the rNDVs were efficient in inducing cellular immune responses to HIV and protective immunity to challenge with vaccinia viruses expressing HIV Env and Gag in mice. These results suggest that the use of a single NDV expressing Env and Gag proteins simultaneously is a novel strategy to develop a safe and effective vaccine against HIV.

2013 ◽  
Vol 29 (2) ◽  
pp. 49-55
Author(s):  
MS Sabrin ◽  
S Saha ◽  
MM Amin ◽  
MG Hossain

Humoral immune responses to Newcastle Disease Virus (NDV) and Bangladesh Agricultural University (BAU) Fowl cholera (BAUFC) vaccines were evaluated in naked neck chickens (NNC). Ten birds were vaccinated with Baby Chick Ranikhet Disease Virus (BCRDV) at Day 7 through intra-ocular route and with Ranikhet Disease Virus (RDV) at day 35 of age through intramuscular route. Serum antibodies were measured by Haemagglutination Inhibition test. Two weeks after final immunization all birds were challenged with virulent field isolate of NDV where all vaccinated birds survived without illness during ten days, and all ten control birds died. Ten birds were vaccinated with BAUFC vaccine at Day 42 and 70 according to the Manufacturer’s instruction, which induced detectable levels of antibody titre as determined by Passive Haemagglutination Assay (PHA) test. Eight vaccinated birds survived following challenge with virulent fowl cholera isolate two weeks after final vaccination and all ten control birds died. DOI: http://dx.doi.org/10.3329/bvet.v29i2.14342 Bangl. vet. 2012. Vol. 29, No. 2, 49-55


2015 ◽  
Vol 11 (2) ◽  
pp. 504-515 ◽  
Author(s):  
Sunil K Khattar ◽  
Senthilkumar Palaniyandi ◽  
Sweety Samal ◽  
Celia C LaBranche ◽  
David C Montefiori ◽  
...  

2015 ◽  
Vol 90 (3) ◽  
pp. 1682-1686 ◽  
Author(s):  
Sunil K. Khattar ◽  
Anthony L. DeVico ◽  
Celia C. LaBranche ◽  
Aruna Panda ◽  
David C. Montefiori ◽  
...  

Newcastle disease virus (NDV) expressing HIV-1 BaL gp160 was evaluated either alone or with monomeric BaL gp120 and BaL SOSIP gp140 protein in a prime-boost combination in guinea pigs to enhance envelope (Env)-specific humoral and mucosal immune responses. We showed that a regimen consisting of an NDV prime followed by a protein boost elicited stronger serum and mucosal Th-1-biased IgG responses and neutralizing antibody responses than NDV-only immunizations. Additionally, these responses were higher after the gp120 than after the SOSIP gp140 protein boost.


2008 ◽  
Vol 83 (2) ◽  
pp. 584-597 ◽  
Author(s):  
Elena Carnero ◽  
Wenjing Li ◽  
Antonio V. Borderia ◽  
Bruno Moltedo ◽  
Thomas Moran ◽  
...  

ABSTRACT One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8+ T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.


2019 ◽  
Vol 146 (2) ◽  
pp. 531-541 ◽  
Author(s):  
Qi Xu ◽  
Udaya S. Rangaswamy ◽  
Weijia Wang ◽  
Scott H. Robbins ◽  
James Harper ◽  
...  

2018 ◽  
Vol 8 (4) ◽  
pp. e00701 ◽  
Author(s):  
Tingting Zhang ◽  
Mengting Ren ◽  
Chenggang Liu ◽  
Liwen Xu ◽  
Fangfang Wang ◽  
...  

2020 ◽  
Author(s):  
mohsen Keshavarz ◽  
Mir Saeed Ebrahimzadeh ◽  
Seyed Mohammad Miri ◽  
Hassan Dianat-Moghadam ◽  
Seyedeh Sara Ghorbanhosseini ◽  
...  

Abstract Background: Cervical cancer is the most common human papillomavirus (HPV)-related cancer caused by persistent genital high-risk HPV infection. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor.Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME).Results: our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 3 and 9) and increased infiltration of tumor microenvironment with CD11b+myeloid and Gr1+MDSCs cells.Conclusions: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and MDSCs expansion in the tumor microenvironment.


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