An adjuvanted subunit SARS-CoV-2 spike protein vaccine provides protection against Covid-19 infection and transmission

Abstract Recombinant protein approaches offer major promise for safe and effective vaccine prevention of SARS-CoV-2 infection. We developed a recombinant spike protein vaccine (called NARUVAX-C19) and characterized its ability when formulated with a nanoemulsion adjuvant to induce anti-spike antibody and T-cell responses and provide protection including against viral transmission in rodent. In mice, NARUVAX-C19 vaccine administered intramuscularly twice at 21-day interval elicited balanced Th1/Th2 humoral and T-cell responses with high titers of neutralizing antibodies against wild-type (D614G) and delta (B.1.617.2) variants. In Syrian hamsters, NARUVAX-C19 provided complete protection against wild-type (D614G) infection and prevented its transmission to naïve animals placed in the same cage as challenged animals. The results contrasted with only weak protection seen with a monomeric spike receptor binding domain (RBD) vaccine even when formulated with the same adjuvant. These encouraging results warrant ongoing development of this Covid-19 vaccine candidate.

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Adjuvanted SARS-CoV-2 Spike Protein Elicits Neutralizing Antibodies and CD4 T Cell Responses after a Single Immunization in Mice

SSRN Electronic Journal ◽

10.2139/ssrn.3701554 ◽

2020 ◽

Author(s):

Katharina Wørzner ◽

Daniel J. Sheward ◽

Signe Tandrup Schmidt ◽

Leo Hanke ◽

Julie Zimmermann ◽

...

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

T Cell Responses ◽

Cd4 T Cell ◽

Spike Protein ◽

Cell Responses

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Polyfunctional CD8+ T-Cell Response to Autologous Peptides from Protease and Reverse Transcriptase of HIV-1 Clade B

Current HIV Research ◽

10.2174/1570162x17666191017105910 ◽

2019 ◽

Vol 17 (5) ◽

pp. 350-359

Author(s):

Liliana Acevedo-Saenz ◽

Federico Perdomo-Celis ◽

Carlos J. Montoya ◽

Paula A. Velilla

Keyword(s):

T Cell ◽

Reverse Transcriptase ◽

Cellular Response ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Response ◽

Effective Vaccine ◽

Cell Responses ◽

Clade B ◽

Hiv 1

Background: : The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles. Objective:: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT). Methods:: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles. Results:: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1β. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia. Conclusion:: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.

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Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽

10.3390/vaccines9040307 ◽

2021 ◽

Vol 9 (4) ◽

pp. 307

Author(s):

Yong Bok Seo ◽

You Suk Suh ◽

Ji In Ryu ◽

Hwanhee Jang ◽

Hanseul Oh ◽

...

Keyword(s):

T Cell ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Dependent Manner ◽

Viral Loads ◽

Cell Responses ◽

Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

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HIV mRNA Vaccines—Progress and Future Paths

Vaccines ◽

10.3390/vaccines9020134 ◽

2021 ◽

Vol 9 (2) ◽

pp. 134

Author(s):

Zekun Mu ◽

Barton F. Haynes ◽

Derek W. Cain

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Vaccination Strategy ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cytotoxic T Cell ◽

Therapeutic Vaccines ◽

Cell Responses ◽

Broadly Neutralizing Antibody ◽

Cytotoxic T Cell Responses

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

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Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Naïve Mice and Those with Preexisting Immunity

Clinical and Vaccine Immunology ◽

10.1128/cvi.05319-11 ◽

2011 ◽

Vol 19 (1) ◽

pp. 84-95 ◽

Cited By ~ 6

Author(s):

Jin Huk Choi ◽

Joe Dekker ◽

Stephen C. Schafer ◽

Jobby John ◽

Craig E. Whitfill ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Neutralizing Antibodies ◽

T Cell Responses ◽

Transduction Efficiency ◽

Virus Antibody ◽

Cell Responses

ABSTRACTThe immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity.In vitroandin vivoassays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P= 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.

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Human T cell responses to the antigen ESAT-6 characterize vaccine candidate and potential diagnostic test for tuberculosis

Journal of Infection ◽

10.1016/s0163-4453(99)90139-1 ◽

1999 ◽

Vol 39 (1) ◽

pp. A9

Author(s):

A. Lalvani ◽

A. Pathan ◽

R. Brookes ◽

H. Pritchard ◽

R. Wilkinson ◽

...

Keyword(s):

T Cell ◽

Diagnostic Test ◽

Vaccine Candidate ◽

T Cell Responses ◽

Cell Responses ◽

Human T Cell

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Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice

Vaccines ◽

10.3390/vaccines7030078 ◽

2019 ◽

Vol 7 (3) ◽

pp. 78 ◽

Cited By ~ 7

Author(s):

Athina Kilpeläinen ◽

Narcís Saubi ◽

Núria Guitart ◽

Alex Olvera ◽

Tomáš Hanke ◽

...

Keyword(s):

T Cell ◽

Miliary Tuberculosis ◽

T Cell Responses ◽

T Cell Response ◽

Expression Vectors ◽

Effective Vaccine ◽

Vaccine Platform ◽

Cell Responses ◽

Hiv 1 ◽

Recombinant Bcg

Despite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has been used as a vaccine vehicle to express both HIV-1 and Simian Immunodeficiemcy Virus (SIV) immunogens. In this study, we constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HTI.int, expressing the HIVACAT T-cell immunogen (HTI). The plasmid was transformed into a lysine auxotrophic Mycobacterium bovis BCG strain (BCGΔLys) to generate the vaccine BCG.HTI2auxo.int. The DNA sequence coding for the HTI immunogen and HTI protein expression were confirmed, and working vaccine stocks were genetically and phenotypically characterized. We demonstrated that the vaccine was stable in vitro for 35 bacterial generations, and that when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in adult BALB/c mice, it was well tolerated and induced HIV-1-specific T-cell responses. Specifically, priming with BCG.HTI2auxo.int doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth. The use of integrative expression vectors and novel HIV-1 immunogens can aid in improving mycobacterial vaccine stability as well as specific immunogenicity. This vaccine candidate may be a useful tool in the development of an effective vaccine platform for priming protective responses against HIV-1/TB and other prevalent pediatric pathogens.

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Potent HIV-1-Specific CD8 T Cell Responses Induced in Mice after Priming with a Multiepitopic DNA-TMEP and Boosting with the HIV Vaccine MVA-B

Viruses ◽

10.3390/v10080424 ◽

2018 ◽

Vol 10 (8) ◽

pp. 424 ◽

Cited By ~ 5

Author(s):

Beatriz Perdiguero ◽

Suresh C. Raman ◽

Cristina Sánchez-Corzo ◽

Carlos Oscar S. Sorzano ◽

José Ramón Valverde ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Response ◽

Effective Vaccine ◽

T Cell Epitopes ◽

Cell Responses ◽

Modified Vaccinia Virus Ankara ◽

Hiv 1

An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B protein contained conserved regions from Gag, Pol, and Nef proteins including multiple CD4 and CD8 T cell epitopes functionally associated with HIV control. Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell responses with broader epitope recognition and higher polyfunctional profile than the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations. Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell response was significantly compromised in DNA-TMEP-primed animals. Our results revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and supported the application of these combined vectors in HIV-1 prevention and/or therapy.

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