E2 multimeric scaffolds displaying HIV-1 Envelope regions elicit V3 and MPER-specific neutralizing antibody and T cell responses when combined with gp160 plasmid DNA

Background : We investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein. Methods : Two open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19-55 years. GX-19 trial participants received two vaccine injections (1.5 mg or 3.0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3.0 mg vaccine injections four weeks apart. Findings : Between June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52.5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1.5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85.74, 144.20, and 201.59 in the 1.5 mg, 3.0 mg GX-19 groups and the 3.0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variants Interpretation : GX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants. Funding : This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea).

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Superior Induction of T Cell Responses to Conserved HIV-1 Regions by Electroporated Alphavirus Replicon DNA Compared to That with Conventional Plasmid DNA Vaccine

Journal of Virology ◽

10.1128/jvi.06535-11 ◽

2012 ◽

Vol 86 (8) ◽

pp. 4082-4090 ◽

Cited By ~ 44

Author(s):

Maria L. Knudsen ◽

Alice Mbewe-Mvula ◽

Maximillian Rosario ◽

Daniel X. Johansson ◽

Maria Kakoulidou ◽

...

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Plasmid Dna ◽

T Cell Responses ◽

Cell Responses ◽

Plasmid Dna Vaccine ◽

Hiv 1

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In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses

Vaccine ◽

10.1016/j.vaccine.2017.03.006 ◽

2017 ◽

Vol 35 (16) ◽

pp. 2042-2051 ◽

Cited By ~ 2

Author(s):

Xun Huang ◽

Qianqian Zhu ◽

Xiaoxing Huang ◽

Lifei Yang ◽

Yufeng Song ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cd8 T Cell ◽

In Vivo Electroporation ◽

Cell Responses ◽

Hiv 1

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Amplification of T-cell responses in DNA-based immunization with HIV-1 Nef by coinjection with a GM-CSF expression vector

Immunology Letters ◽

10.1016/s0165-2478(97)88025-x ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 294-295

Author(s):

C Svanholm

Keyword(s):

T Cell ◽

Expression Vector ◽

T Cell Responses ◽

Gm Csf ◽

Cell Responses ◽

Hiv 1

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Faculty Opinions recommendation of A dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1 replication.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717972955.793495235 ◽

2014 ◽

Author(s):

Angus Dalgleish

Keyword(s):

T Cell ◽

Dendritic Cell ◽

T Cell Responses ◽

Cell Responses ◽

Hiv 1 ◽

Dendritic Cell Based Vaccine

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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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