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

Vaccines ◽  
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.

scholarly journals Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

2021 ◽  
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 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 indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

scholarly journals 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 ◽  
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.

scholarly journals Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

2021 ◽  
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anatomical Site ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

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.

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

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.

scholarly journals The Immunogenic and Immunoprotective Activities of Recombinant Chimeric T. gondii Proteins Containing AMA1 Antigen Fragments

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 724
Author(s):  
Justyna Gatkowska ◽  
Katarzyna Dzitko ◽  
Bartłomiej Tomasz Ferra ◽  
Lucyna Holec-Gąsior ◽  
Malwina Kawka ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Chimeric Proteins ◽  
Universal Vaccine ◽  
New Approach ◽  
Partial Protection ◽  
Cellular Immune Responses ◽  
Specific Igg ◽  
Cellular Immune

Toxoplasmosis, one of the most common parasitoses worldwide, is potentially dangerous for individuals with a weakened immune system, but specific immunoprophylaxis intended for humans is still lacking. Thus, efforts have been made to create an efficient universal vaccine for both animals and humans to overcome the shortcomings of currently used treatment methods and protect all hosts against toxoplasmosis. The current work represents a relatively new approach to vaccine development based on recombinant chimeric Toxoplasma gondii antigens. In the present research, three tetravalent chimeric proteins containing different portions of the parasite’s AMA1 antigen—AMA1domainI-SAG2-GRA1-ROP1L (ANSGR), AMA1domainsII,III-SAG2-GRA1-ROP1L (ACSGR) and AMA1fullprotein-SAG2-GRA1-ROP1L (AFSGR)—were tested for their immunogenic and immunoprotective capacities. All tested proteins were immunogenic, as evidenced by the triggering of specific humoral and cellular immune responses in vaccinated C3H/HeOuJ mice, defined by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and synthesis of key Th1/Th2 cytokines by Toxoplasma lysate antigen-stimulated splenocytes in vitro. Although all tested preparations provided partial protection against chronic toxoplasmosis in immunized and T. gondii-challenged mice, the intensity of the generated immunoprotection depended on the fragment of the AMA1 antigen incorporated into the chimeric antigen’s structure.

scholarly journals Immunogenicity and reactogenicity of a heterologous COVID-19 prime-boost vaccination compared with homologous vaccine regimens

2021 ◽  
Author(s):  
Tina Schmidt ◽  
Verena Klemis ◽  
David Schub ◽  
Janine Mihm ◽  
Franziska Hielscher ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Expression Profiling ◽  
Neutralizing Antibodies ◽  
Cd8 T Cell ◽  
Vector Vaccine ◽  
Cellular Immune Responses ◽  
Specific Igg ◽  
Cellular Immune ◽  
Polyfunctional T Cells

Heterologous priming with the ChAdOx1-nCoV-19 vector-vaccine followed by boosting with an mRNA-vaccine is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. Here we show that the heterologous regimen induced spike-specific IgG, neutralizing antibodies, and spike-specific CD4 T-cells, which were significantly more pronounced than after homologous vector boost, and higher or comparable in magnitude to the homologous mRNA regimens. Moreover, spike-specific CD8 T-cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Cytokine expression profiling showed a predominance of polyfunctional T-cells expressing IFNγ, TNFα and IL-2 with subtle differences between regimens. Both recipients of the homologous vector-regimen and the heterologous vector/mRNA-combination were most affected by the priming vector-vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA-boosting. Taken together, heterologous vector-mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profile. This knowledge will have implications for future vaccine strategies.

scholarly journals CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

2021 ◽  
Author(s):  
Yiru Long ◽  
Jianhua Sun ◽  
Tingting Liu ◽  
Feng Tang ◽  
Xinxin Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Herd Immunity ◽  
Peptide Vaccine ◽  
Cell Responses ◽  
High Efficient ◽  
T Cell Immune Responses ◽  
Cellular Immune

AbstractSafe, economical and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and halt the pandemic. We have constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains two immunodominant peptides screened from receptor-binding domain (RBD) and is fully chemically synthesized. And the vaccine has optimized nanoemulsion formulation, outstanding stability and safety. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of RBD-specific and protective neutralizing antibodies (NAbs), which were also effective to RBD mutations. CoVac501 was found to elicit the increase of memory T cells, antigen-specific CD8+ T cell responses and Th1-biased CD4+ T cell immune responses in NHPs. More importantly, the sera from the immunized NHPs can prevent infection of live SARS-CoV-2 in vitro.One-Sentence SummaryA novel SARS-CoV-2 vaccine we developed, CoVac501, which is a fully chemically synthesized and self-adjuvanting peptides conjugated with TLR7 agonists, can induce high-efficient humoral and cellular immune responses against SARS-CoV-2.

scholarly journals Immunogenicity of Low-Dose Prime-Boost Vaccination of mRNA Vaccine CV07050101 in Non-Human Primates

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1645
Author(s):  
Neeltje van Doremalen ◽  
Robert J. Fischer ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Brian J. 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 at two and four weeks after prime vaccination. Two weeks after boost vaccination, binding but no neutralizing antibodies were detected in four out of six non-human primates. SARS-CoV-2 S protein-specific T cell responses were detected in these four animals. In conclusion, prime-boost vaccination with 4 µg of vaccine candidate CV07050101 resulted in limited immune responses in four out of six non-human primates.

scholarly journals Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model

2021 ◽  
Author(s):  
Sheng Jiang ◽  
Shuting Wu ◽  
Gan Zhao ◽  
Yue He ◽  
Linlin Bao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Phase Iii ◽  
Protective Effects ◽  
Cytotoxic Lymphocyte ◽  
Live Virus ◽  
Cellular Immune Responses ◽  
Cellular Immune

COVID-19 caused by SARS-CoV-2 has been spreading worldwide. To date, several vaccine candidates moved into EUA or CA applications. Although DNA vaccine is on phase III clinical trial, it is a promised technology platform with many advantages. Here, we showed that the pGX9501 DNA vaccine encoded the spike full-length protein-induced strong humoral and cellular immune responses in mice with higher neutralizing antibodies, blocking the hACE2-RBD binding against live virus infection in vitro. Importantly, higher levels of IFN-γ expression in CD8+ and CD4+ T cell and specific cytotoxic lymphocyte (CTL) killings effect were also observed in the pGX9501-immunized group. It provided subsequent protection against virus challenges in the hACE2 transgenic mouse model. Overall, pGX9501 was a promising DNA vaccine candidate against COVID-19, inducing strong humoral immunity and cellular immunity that contributed to the vaccine's protective effects.

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