In a recently published study bioRxiv* Preprint servers, researchers in Italy and the United States evaluated the efficacy and immunogenicity of an adjuvanted COVID-19 quadrivalent vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) Protein Subunit 1 (S1). .
Composed of the Wuhan Hu-1 strain and SARS-CoV-2 variants of concern (VOCs) alpha, beta and gamma S1 proteins in a non-human primate model (NHP) of rhesus monkey (RM) with controlled Monkey Immunodeficiency Virus (SIV) infection.
background
Coronavirus disease 2019 (COVID-19) vaccines have been effective in reducing morbidity and mortality associated with SARS-CoV-2 infection. However, the continued emergence of increasingly transmissible and immune-vasive VOCs has compromised the effectiveness of the vaccine. Therefore, updated multivalent vaccines that confer durable and broad immune protection are needed to contain COVID-19.
Protein subunit-type COVID-19 vaccines are reported to be safe and immunogenic, easy to mass-produce, distribute, store and transport, and have shown success against other viruses such as hepatitis B virus (HBV). The properties make the vaccine type ideal candidates for global vaccine equity, particularly for nations that have limited access to viral vector-based and messenger ribonucleic acid (mRNA) vaccines.
The study authors have previously demonstrated the immunogenicity of S1-targeted vaccines against several β-CoVs, including SARS-CoV, SARS-CoV-2 and Middle East Respiratory Syndrome-CoV (MERS-CoV).
About the study
In the present study, researchers evaluate the immunogenicity of a quadrivalent SARS-CoV-2 S1 vaccine targeting Wuhan-Hu-1, Alpha, Beta and Gamma S1 among RMs; infected with SIV.
The team profiled lymphocyte responses to vaccination for two months after the first primary vaccination by counting B and T lymphocytes. They examined the concentrations of T-lymphocyte activation markers and the number of subsets of memory lymphocytes among peripheral blood mononuclear cells (PBMCs). Activation markers such as the differentiation cluster (CD)-38, -69 and the human leukocyte antigen DR isotype (HLA-DR) were used for the analysis.
In addition, expression of the Ki-67 proliferation marker was assessed. Prior to vaccination, RMs were infected with SIVs that naturally infect African green monkeys (SIVsab). RMs were given primary and booster doses at week 3.0 with recombinant SARS-CoV-2 Wuhan Hu-1, alpha, beta and gamma spike proteins mixed with the squalene-based adjuvant AddaVaxTM. Vectors expressing recombinant SARS-CoV-2 proteins were constructed and the plasmid constructs were confirmed by deoxyribonucleic acid (DNA) sequencing.
The proteins were then purified and transiently expressed in Expi293 cells. Transfection experiments were performed, after which the supernatants were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot (WB) analyses. Rhesus monkey peripheral blood mononuclear cells (RM-PMBCs) were isolated on days 1.0, 3.0, 7.0, 10.0, 14.0, 21.0, 24.0, 28.0, 31.0, 35.0, 42.0, 49.0 and 64.0 days after the main vaccination. Anti-Wuhan Hu-1 immunoglobulin G (IgG) serological antibody endpoint titers (EPT) were determined using enzyme-linked immunosorbent assays (ELISA).
Furthermore, microneutralization assays (NT90) were performed to evaluate the SARS-CoV-2 neutralizing ability of vaccinated RM sera. Inhibition of binding between the angiotensin converting enzyme-2 (ACE2) and the trimeric S-proteins of SARS-CoV-2 VOCs, including the sub-VOCs of Omicron (BA.2 sub-VOC, BA.3 sub- VOC, BA.1 sub-VOC with R246K mutation and BA.1 sub-VOC with L452R mutation).
The team performed intracellular cytokine staining to assess anti-ST lymphocyte responses in hyper- and cytotoxic T lymphocytes. In addition, levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) cytokines were determined. Flow cytometry was carried out for the absolute determination of the serological immunological cell numbers.
Results
The tetravalent vaccine approach induced cellular and humoral immunological responses, with B and T lymphocyte responses peaking mainly after booster vaccinations. In addition, the tetravalent vaccine elicited cross-reactive and neutralizing antibodies, angiotensin converting enzyme 2 – Blocking antibodies (ACE2-blocking antibodies) and cell-mediated reactions, including S-directed CD4+ T (helper T) lymphocytes.
The tetravalent vaccine could induce ACE2-blocking and Omicron S-binding antibodies without Omicron vaccination, suggesting broad immune protection against the SARS-CoV-2 variants.
The vaccine also elicited antibodies against the wild-type (WT), beta and delta variants. Ant-S-CD4+ T lymphocyte responses were observed in RM-PBMCs with variable cytokine levels after 42.0 days of primary vaccination. However, no CD8+ T (cytotoxic T) lymphocyte reactions were observed. The number of CD8+ T-lymphocytes was most increased after the booster vaccination. Increased CD38, CD69, Ki-67 and HLA-DR expression was observed among T lymphocyte subsets.
Decreased levels of helper and central memory cytotoxic (CM) T lymphocytes, helper T and cytotoxic T-naïve T lymphocytes were observed after the primary and booster vaccinations.
In contrast, the number of helper and cytotoxic effector memory (EM) T lymphocytes increased after prime-boost vaccination. The results suggest that the vaccine candidate has changed from a CM phenotype to an EM phenotype, which could aid in the development of more robust and rapid vaccine responses.
Diploma
Study results showed that the tetravalent vaccine approach conferred broad immune protection against multiple SARS-CoV-2 variants. Findings could inform vaccine development to reduce the global health burden of COVID-19.
quotes
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APA
Toshniwal Paharia, Pooja Toshniwal Paharia. (2023, March 21). Tetravalent COVID vaccine offers broad antibody responses against SARS-CoV-2 variants in animal model. News Medical. Retrieved March 22, 2023 from https://www.news-medical.net/news/20230321/Tetravalent-COVID-vaccine-provides-broad-antibody-responses-against-SARS-CoV-2-variants-in-animal -model.aspx.
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MLA
Toshniwal Paharia, Pooja Toshniwal Paharia. “COVID quadrivalent vaccine offers broad antibody responses against SARS-CoV-2 variants in animal model.” News Medical. March 22, 2023.
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Chicago
Toshniwal Paharia, Pooja Toshniwal Paharia. “COVID quadrivalent vaccine offers broad antibody responses against SARS-CoV-2 variants in animal model.” News Medical. https://www.news-medical.net/news/20230321/Tetravalent-COVID-vaccine-provides-broad-antibody-responses-against-SARS-CoV-2-variants-in-animal-model.aspx. (accessed March 22, 2023).
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Harvard
Toshniwal Paharia, Pooja Toshniwal Paharia. 2023 Tetravalent COVID vaccine offers broad antibody responses against SARS-CoV-2 variants in animal model. News-Medical, accessed March 22, 2023, https://www.news-medical.net/news/20230321/Tetravalent-COVID-vaccine-provides-broad-antibody-responses-against-SARS-CoV-2-variants -in-animal-model.aspx.
