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Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity.
Front Immunol. 2021; 12:719077.FI

Abstract

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world's population at record speeds. However, there is still a demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the SARS-CoV-2 spike protein (SV.Spike), combined with the OX40 immunostimulatory antibody (αOX40) as a novel, highly effective vaccine approach. We show that SV.Spike plus αOX40 elicits long-lasting neutralizing antibodies and a vigorous T-cell response in mice. Protein binding, immunohistochemical, and cellular infection assays all show that vaccinated mice sera inhibits spike functions. Immunophenotyping, RNA Seq transcriptome profiles, and metabolic analysis indicate a reprogramming of T cells in vaccinated mice. Activated T cells were found to mobilize to lung tissue. Most importantly, SV.Spike plus αOX40 provided robust immune protection against infection with authentic coronavirus in transgenic mice expressing the human ACE2 receptor (hACE2-Tg). Finally, our immunization strategy induced strong effector memory response, potentiating protective immunity against re-exposure to SARS-CoV-2 spike protein. Our results show the potential of a new Sindbis virus-based vaccine platform to counteract waning immune response, which can be used as a new candidate to combat SARS-CoV-2. Given the T-cell responses elicited, our vaccine is likely to be effective against variants that are proving challenging, as well as serve as a platform to develop a broader spectrum pancoronavirus vaccine. Similarly, the vaccine approach is likely to be applicable to other pathogens.

Authors+Show Affiliations

Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.Department of Microbiology, New York University Grossman School of Medicine, New York, NY, United States.Department of Microbiology, New York University Grossman School of Medicine, New York, NY, United States.Department of Microbiology, New York University Grossman School of Medicine, New York, NY, United States.Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34394127

Citation

Scaglione, Antonella, et al. "Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity." Frontiers in Immunology, vol. 12, 2021, p. 719077.
Scaglione A, Opp S, Hurtado A, et al. Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity. Front Immunol. 2021;12:719077.
Scaglione, A., Opp, S., Hurtado, A., Lin, Z., Pampeno, C., Noval, M. G., Thannickal, S. A., Stapleford, K. A., & Meruelo, D. (2021). Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity. Frontiers in Immunology, 12, 719077. https://doi.org/10.3389/fimmu.2021.719077
Scaglione A, et al. Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity. Front Immunol. 2021;12:719077. PubMed PMID: 34394127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity. AU - Scaglione,Antonella, AU - Opp,Silvana, AU - Hurtado,Alicia, AU - Lin,Ziyan, AU - Pampeno,Christine, AU - Noval,Maria G, AU - Thannickal,Sara A, AU - Stapleford,Kenneth A, AU - Meruelo,Daniel, Y1 - 2021/07/29/ PY - 2021/06/01/received PY - 2021/07/13/accepted PY - 2021/8/16/entrez PY - 2021/8/17/pubmed PY - 2021/8/26/medline KW - COVID19 KW - SARS-CoV-2 immunity KW - SARS-CoV-2 vaccine KW - Sindbis virus vaccine KW - alphavirus vaccine KW - synergistic combination SARS-CoV-2 vaccine strategy KW - αOX40 SP - 719077 EP - 719077 JF - Frontiers in immunology JO - Front Immunol VL - 12 N2 - The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world's population at record speeds. However, there is still a demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the SARS-CoV-2 spike protein (SV.Spike), combined with the OX40 immunostimulatory antibody (αOX40) as a novel, highly effective vaccine approach. We show that SV.Spike plus αOX40 elicits long-lasting neutralizing antibodies and a vigorous T-cell response in mice. Protein binding, immunohistochemical, and cellular infection assays all show that vaccinated mice sera inhibits spike functions. Immunophenotyping, RNA Seq transcriptome profiles, and metabolic analysis indicate a reprogramming of T cells in vaccinated mice. Activated T cells were found to mobilize to lung tissue. Most importantly, SV.Spike plus αOX40 provided robust immune protection against infection with authentic coronavirus in transgenic mice expressing the human ACE2 receptor (hACE2-Tg). Finally, our immunization strategy induced strong effector memory response, potentiating protective immunity against re-exposure to SARS-CoV-2 spike protein. Our results show the potential of a new Sindbis virus-based vaccine platform to counteract waning immune response, which can be used as a new candidate to combat SARS-CoV-2. Given the T-cell responses elicited, our vaccine is likely to be effective against variants that are proving challenging, as well as serve as a platform to develop a broader spectrum pancoronavirus vaccine. Similarly, the vaccine approach is likely to be applicable to other pathogens. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/34394127/Combination_of_a_Sindbis_SARS_CoV_2_Spike_Vaccine_and_αOX40_Antibody_Elicits_Protective_Immunity_Against_SARS_CoV_2_Induced_Disease_and_Potentiates_Long_Term_SARS_CoV_2_Specific_Humoral_and_T_Cell_Immunity_ L2 - https://doi.org/10.3389/fimmu.2021.719077 DB - PRIME DP - Unbound Medicine ER -