scholarly journals BoHV-1-Vectored BVDV-2 Subunit Vaccine Induces BVDV Cross-Reactive Cellular Immune Responses and Protects against BVDV-2 Challenge

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 46
Author(s):  
Shafiqul I. Chowdhury ◽  
Katrin Pannhorst ◽  
Neha Sangewar ◽  
Selvaraj Pavulraj ◽  
Xue Wen ◽  
...  

The bovine respiratory disease complex (BRDC) remains a major problem for both beef and dairy cattle industries worldwide. BRDC frequently involves an initial viral respiratory infection resulting in immunosuppression, which creates a favorable condition for fatal secondary bacterial infection. Current polyvalent modified live vaccines against bovine herpesvirus type 1(BoHV-1) and bovine viral diarrhea virus (BVDV) have limitations concerning their safety and efficacy. To address these shortcomings and safety issues, we have constructed a quadruple gene mutated BoHV-1 vaccine vector (BoHV-1 QMV), which expresses BVDV type 2, chimeric E2 and Flag-tagged Erns-fused with bovine granulocyte monocyte colony-stimulating factor (GM-CSF) designated here as QMV-BVD2*. Here we compared the safety, immunogenicity, and protective efficacy of QMV-BVD2* vaccination in calves against BVDV-2 with Zoetis Bovi-shield Gold 3 trivalent (BoHV-1, BVDV types 1 and 2) vaccine. The QMV-BVD2* prototype subunit vaccine induced the BoHV-1 and BVDV-2 neutralizing antibody responses along with BVDV-1 and -2 cross-reactive cellular immune responses. Moreover, after a virulent BVDV-2 challenge, the QMV-BVD2* prototype subunit vaccine conferred a more rapid recall BVDV-2-specific neutralizing antibody response and considerably better recall BVDV types 1 and 2-cross protective cellular immune responses than that of the Zoetis Bovi-shield Gold 3.

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 350
Author(s):  
Zhanhui Wang ◽  
Mengyao Liu ◽  
Haoran Zhao ◽  
Pengpeng Wang ◽  
Wenge Ma ◽  
...  

Bovine viral diarrhea virus (BVDV) is an important animal pathogen that affects cattle. Infections caused by the virus have resulted in substantial economic losses and outbreaks of BVDV are reported globally. Virus-like particles (VLPs) are promising vaccine technology largely due to their safety and strong ability to elicit robust immune responses. In this study, we developed a strategy to generate BVDV-VLPs using a baculovirus expression vector system (BEVS). We were able to assemble BVDV-VLPs composed of dimerized viral proteins E2 and Erns, and the VLPs were spherical particles with the diameters of about 50 nm. Mice immunized with 15 μg of VLPs adjuvanted with ISA201 elicited higher levels of E2-specific IgG, IgG1, and IgG2a antibodies as well as higher BVDV-neutralizing activity in comparison with controls. Re-stimulation of the splenocytes collected from mice immunized with VLPs led to significantly increased levels of CD3+CD4+T cells and CD3+CD8+T cells. In addition, the splenocytes showed dramatically enhanced proliferation and the secretion of Th1-associated IFN-γ and Th2-associated IL-4 compared to that of the unstimulated control group. Taken together, our data indicate that BVDV-VLPs efficiently induced BVDV-specific humoral and cellular immune responses in mice, showing a promising potential of developing BVDV-VLP-based vaccines for the prevention of BVDV infections.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Hua Li ◽  
Guo-Zhen Zhao ◽  
Long-Xin Qiu ◽  
Ai-Ling Dai ◽  
Wang-Wei Wu ◽  
...  

Haemophilus parasuiscan cause Glässer’s disease characterized by fibrinous polyserositis, polyarthritis, and meningitis. The current prevention of Glässer’s disease is mainly based on the inactive vaccines; however, the protective efficacy usually fails in heterogeneous or homologous challenges. Here, the predominant lineage ofH. parasuis(LY02 strain) in Fujian province, China, characterized as serovar 5, was used to evaluate the protective immunity against acuteH. parasuisinfection in piglets after inactivation. Following challenging withH. parasuis,only mild lesions in the pigs immunized with the killed vaccine were observed, whereas the typical symptoms of Glässer’s disease presented in the nonimmunized piglets. A strong IgG immune response was induced by the inactive vaccine. CD4+and CD8+T lymphocyte levels were increased, indicating the potent cellular immune responses were elicited. The significantly high levels of IL-2, IL-4, TGF-β, and IFN-γin sera from pigs immunized with this killed vaccine suggested that the mixed Th1 and Th2 immune responses were induced, associated with the high protection againstH. parasuisinfection compared to the nonimmunized animals. This study indicated that the inactivated LY02 strain ofH. parasuiscould serve as a potential vaccine candidate to prevent the prevalence ofH. parasuisin Fujian province, China.


2004 ◽  
Vol 85 (8) ◽  
pp. 2407-2419 ◽  
Author(s):  
B. Mäkitalo ◽  
P. Lundholm ◽  
J. Hinkula ◽  
C. Nilsson ◽  
K. Karlén ◽  
...  

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.


Vaccine ◽  
1990 ◽  
Vol 8 (5) ◽  
pp. 503-509 ◽  
Author(s):  
Kuniaki Nerome ◽  
Yasuyuki Yoshioka ◽  
Masatoshi Ishida ◽  
Kunio Okuma ◽  
Tetsuya Oka ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1936
Author(s):  
Yi-Sheng Sun ◽  
Jing-Jing Zhou ◽  
Han-Ping Zhu ◽  
Fang Xu ◽  
Wen-Bin Zhao ◽  
...  

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19.


2021 ◽  
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.


2021 ◽  
Author(s):  
C. Sabrina Tan ◽  
Ai-ris Y. Collier ◽  
Jinyan Liu ◽  
Jingyou Yu ◽  
Huahua Wan ◽  
...  

ABSTRACTPrevious studies have reported that a third dose of the BNT162b2 (Pfizer) COVID-19 vaccine increased antibody titers and protective efficacy. Here we compare humoral and cellular immune responses in 65 individuals who were vaccinated with the BNT162b2 vaccine and were boosted after at least 6 months with either Ad26.COV2.S (Johnson & Johnson; N=41) or BNT162b2 (Pfizer; N=24).


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