scholarly journals Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines—A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2290
Author(s):  
Jakob Trimpert ◽  
Susanne Herwig ◽  
Julia Stein ◽  
Daria Vladimirova ◽  
Julia M. Adler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nucleocapsid Protein ◽  
Neutralizing Antibodies ◽  
Specific Antigen ◽  
T Cell Response ◽  
Full Length ◽  
Spike Protein ◽  
Protective Effects ◽  
Cellular Immune Responses ◽  
Cellular Immune

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design.

scholarly journals Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS‑CoV‑2 vaccination

2021 ◽  
Author(s):  
Luise Erpenbeck ◽  
Moritz M. Hollstein ◽  
Lennart Münsterkötter ◽  
Michael Schön ◽  
Armin Bergmann ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Neutralizing Antibodies ◽  
Cell Activation ◽  
Booster Vaccination ◽  
Interferon Γ ◽  
T Cell Response ◽  
Cellular Immune Responses ◽  
Cellular Immune

Background: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, avidity) and cellular (spike-induced T cell interferon‑γ release) immune responses in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Results: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared to BNT162b2 (70±114 vs. 226±279 BAU/ml, p<0.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387±1627 and homologous BNT162b2 3202±2184 vs. homologous ChAdOx1 nCoV-19 413±461 BAU/ml, both p<0.001; spike-induced T cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069±6733 and homologous BNT162b2 4880±7570 vs. homologous ChAdOx1 nCoV-19 1152±2243 mIU/ml, both p<0.001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses.

scholarly journals Simultaneous Administration of Recombinant Measles Viruses Expressing Respiratory Syncytial Virus Fusion (F) and Nucleo (N) Proteins Induced Humoral and Cellular Immune Responses in Cotton Rats

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 27 ◽  
Author(s):  
Yoshiaki Yamaji ◽  
Akihito Sawada ◽  
Yosuke Yasui ◽  
Takashi Ito ◽  
Tetsuo Nakayama
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Simultaneous Administration ◽  
Cellular Immune Responses ◽  
Immunization Group ◽  
Cotton Rats ◽  
Ifn Γ ◽  
Syncytial Virus ◽  
Cellular Immune

We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.

scholarly journals Safety and Immunogenicity of Heterologous and Homologous 2-Dose Regimens of Adenovirus Serotype 26– and Modified Vaccinia Ankara–Vectored Ebola Vaccines: A Randomized, Controlled Phase 1 Study

2020 ◽  
Author(s):  
Neil Goldstein ◽  
Viki Bockstal ◽  
Stephan Bart ◽  
Kerstin Luhn ◽  
Cynthia Robinson ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Phase 1 ◽  
Booster Vaccination ◽  
Controlled Study ◽  
Adenovirus Serotype ◽  
Cellular Immune Responses ◽  
High Doses ◽  
Cellular Immune

Abstract Background This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen.

Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4330-4339 ◽  
Author(s):  
Thushan I. de Silva ◽  
Yanchun Peng ◽  
Aleksandra Leligdowicz ◽  
Irfan Zaidi ◽  
Lucy Li ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
T Cell Response ◽  
Viral Control ◽  
Retroviral Infection ◽  
Cellular Immune Responses ◽  
Key Points ◽  
Cellular Immune ◽  
Insight Into

Key PointsHIV-2 viral control is associated with a polyfunctional Gag-specific CD8+ T-cell response but not with perforin upregulation. Our findings provide insight into cellular immune responses associated with a naturally contained human retroviral infection.

Antitumor Effect of a DNA Vaccine Harboring Prostate Cancer-Specific Antigen with IL-12 as an Intramolecular Adjuvant

2017 ◽  
Vol 27 (3) ◽  
pp. 168-174 ◽  
Author(s):  
Yu Yang ◽  
Zhiqiang Shao ◽  
Jiangping Gao
Keyword(s):  
Prostate Cancer ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Dna Vaccines ◽  
Electric Pulse ◽  
Specific Antigen ◽  
Interleukin 12 ◽  
Cellular Immune Responses ◽  
Prostate Cancer Therapy ◽  
Cellular Immune

To improve the lower immune intensity of DNA vaccines, we developed a DNA vaccine based on prostate cancer-specific antigen (PSA), which has been suggested as a potential target for prostate cancer therapy, and enhanced the DNA vaccine potency using interleukin-12 (IL-12) as an intramolecular adjuvant. A series of DNA plasmids encoding human PSA, IL-12, and their conjugates was constructed and injected into female mice intramuscularly, followed by an electric pulse. The humoral and cellular immune responses after immunization were detected by ELISA and ELISPOT, respectively. To evaluate the therapeutic efficacy of these plasmids, a mouse model with a PSA-expressing tumor was constructed. Mice vaccinated with PSA-IL-12 plasmids elicited the strongest PSA-specific humoral and cellular immune responses. Furthermore, these vaccinations inhibited the growth of PSA-expressing tumors and prolonged mouse survival. These observations emphasize the potential of the IL-12 gene as an intramolecular adjuvant for DNA vaccines. Moreover, the vaccine based on PSA and IL-12 may be a promising treatment for prostate cancer.

scholarly journals BacMam virus-based surface display for HCV E2 glycoprotein induces strong cross-neutralizing antibodies and cellular immune responses in vaccinated mice

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ebrahim Kord ◽  
Farzin Roohvand ◽  
Jean Dubuisson ◽  
Thibaut Vausselin ◽  
Hosein Nasr Azadani ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Surface Display ◽  
Immunogold Electron Microscopy ◽  
Cellular Immune Responses ◽  
Boost Immunization ◽  
Ifn Γ ◽  
Cellular Immune ◽  
And Control

Abstract Background Despite recent advancements, limitations in the treatment and control of hepatitis C virus (HCV) infection reprioritized the studies for invention of an efficient HCV vaccine to elicit strong neutralizing antibodies (NAbs) and cellular responses. Methods Herein, we report molecular construction of a BacMam virus-based surface display for a subtype-1a HCV gpE2 (Bac-CMV-E2-gp64; Bac) that both expressed and displayed gpE2 in mammalian cells and bacouloviral envelope, respectively. Results Assessments by western blotting, Immunofluorescence and Immunogold-electron microscopy indicated the proper expression and incorporation in insect cell and baculovirus envelope, respectively. Mice immunized in three different prime-boost immunization groups of: Bac/Bac, Bac/Pro (bacoulovirus-derived gpE2) and Bac/DNA (plasmid DNA (pCDNA)-encoding gpE2) developed high levels of IgG and IFN-γ (highest for Bac/Bac group) indicating the induction of both humeral and cellular immune responses. Calculation of the IgG2a/IgG1 and IFN-γ/IL-4 ratios indicated a Th1 polarization of immune responses in the Bac/Bac and Bac/DNA groups but a balanced Th1-Th2 phenotype in the Bac/Pro group. Sera of the mice in the Bac/Bac group provided the highest percentage of cross-NAbs against a subtype-2a HCVcc (JFH1) compared to Bac/Pro and Bac/DNA groups (62% versus 41% and 6%). Conclusions Results indicated that BacMam virus-based surface display for gpE2 might act as both subunit and DNA vaccine and offers a promising strategy for development of HCV vaccine for concurrent induction of strong humoral and cellular immune responses.

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

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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