Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

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A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽

10.3390/vaccines9121408 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1408

Author(s):

Qiao Li ◽

Zhihua Liu ◽

Yi Liu ◽

Chen Liang ◽

Jiayi Shu ◽

...

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Inbred Mouse ◽

Effective Vaccine ◽

Mouse Strains ◽

Cellular Immune Responses ◽

Recombinant Hbsag ◽

Cellular Immune

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.

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VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants

Vaccines ◽

10.3390/vaccines9121409 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1409

Author(s):

Wasim A. Prates-Syed ◽

Lorena C. S. Chaves ◽

Karin P. Crema ◽

Larissa Vuitika ◽

Aline Lira ◽

...

Keyword(s):

Immune Responses ◽

Immune Evasion ◽

Convergent Evolution ◽

Vaccine Development ◽

Receptor Binding Domain ◽

Vaccine Platform ◽

Cellular Immune Responses ◽

Alpha Beta ◽

Cellular Immune ◽

Financial Losses

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology.

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Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

PLoS ONE ◽

10.1371/journal.pone.0022718 ◽

2011 ◽

Vol 6 (7) ◽

pp. e22718 ◽

Cited By ~ 22

Author(s):

Suraj B. Sable ◽

Mani Cheruvu ◽

Subhadra Nandakumar ◽

Sunita Sharma ◽

Kakali Bandyopadhyay ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Vaccine Candidates ◽

Cellular Immune Responses ◽

Cellular Immune

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Humoral and cellular immunity and the safety of COVID-19 vaccines: a summary of data published by 21 May 2021

International Immunology ◽

10.1093/intimm/dxab061 ◽

2021 ◽

Vol 33 (10) ◽

pp. 529-540

Author(s):

Kun Xu ◽

Lianpan Dai ◽

George F Gao

Keyword(s):

Immune Responses ◽

Viral Genome ◽

Vaccine Development ◽

Published Data ◽

Humoral And Cellular Immunity ◽

Cellular Immune Responses ◽

Rapid Responses ◽

Study Results ◽

Protection Efficacy ◽

Cellular Immune

Abstract Coronavirus disease 2019 (COVID-19) has caused millions of deaths, and serious consequences to public health, economies and societies. Rapid responses in vaccine development have taken place since the isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the release of the viral genome sequence. By 21 May 2021, 101 vaccines were under clinical trials, and published data were available for 18 of them. Clinical study results from some vaccines indicated good immunogenicity and acceptable reactogenicity. Here, we focus on these 18 vaccines that had published clinical data to dissect the induced humoral and cellular immune responses as well as their safety profiles and protection efficacy.

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Immunogenicity of low dose prime-boost vaccination of mRNA vaccine CV07050101 in non-human primates

10.1101/2021.07.07.451505 ◽

2021 ◽

Author(s):

Neeltje van Doremalen ◽

Robert Fischer ◽

Jonathan Schulz ◽

Myndi Holbrook ◽

Brian Smith ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Small Animal ◽

S Protein ◽

Cell Responses ◽

Cellular Immune Responses ◽

Boost Vaccination ◽

Human Volunteers ◽

Cellular Immune

Many different vaccine candidates against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of COVID-19, are currently approved and under development. Vaccine platforms vary from mRNA vaccines to viral-vectored vaccines, and several candidates have been shown to produce humoral and cellular responses in small animal models, non-human primates and human volunteers. In this study, six non-human primates received a prime-boost intramuscular vaccination with 4 μg of mRNA vaccine candidate CV07050101, which encodes a pre-fusion stabilized spike (S) protein of SARS-CoV-2. Boost vaccination was performed 28 days post prime vaccination. As a control, six animals were similarly injected with PBS. Humoral and cellular immune responses were investigated at time of vaccination, and two weeks afterwards. No antibodies could be detected two and four weeks after prime vaccination. Two weeks after boost vaccination, binding but no neutralizing antibodies were detected in 4 out of 6 non-human primates. SARS-CoV-2 S protein specific T cell responses were detected in these 4 animals. In conclusion, prime-boost vaccination with 4 μg of vaccine candidate CV07050101 resulted in limited immune responses in 4 out of 6 non-human primates.

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Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

Vaccines ◽

10.3390/vaccines9080852 ◽

2021 ◽

Vol 9 (8) ◽

pp. 852

Author(s):

Khalid A. Alluhaybi ◽

Rahaf H. Alharbi ◽

Rowa Y. Alhabbab ◽

Najwa D. Aljehani ◽

Sawsan S. Alamri ◽

...

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Cell Responses ◽

Cellular Immune Responses ◽

Specific Igg ◽

Cellular Immune ◽

Different Doses

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

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Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

10.21203/rs.3.rs-40198/v1 ◽

2020 ◽

Author(s):

Flavia Chiuppesi ◽

Marcela d’Alincourt Salazar ◽

Heidi Contreras ◽

Vu Nguyen ◽

Joy Martinez ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Candidate ◽

Vaccine Platform ◽

Synthetic Dna ◽

Cellular Immune Responses ◽

Global Pandemic ◽

Immunodominant Antigens ◽

Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

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