In monkeys, spike-based vaccines generate some immunity based on CD8 T cells

Scientists around the world are continuously working to develop effective coronavirus disease 2019 (COVID-19) vaccines and treatments. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants such as Omicron and Delta has decreased significantly. efficacy of available vaccine.

study: CD8 T cells contribute to vaccine protection against SARS-CoV-2 in monkeys. Image Credit: Dotted Yeti / Shutterstock.com

Background

The effectiveness of COVID-19 vaccines is often determined by the level of antibody response induced after vaccination. Preclinical and clinical studies suggest that CD8+ T cell responses are also associated with innate immune protection against SARS-CoV-2, especially when antibodies provide only partial protection.

For cell-mediated immune responses, Neutralizing antibody (nAb) Response to SARS-CoV-2 variants. Importantly, both messenger ribonucleic acid (mRNA) and adenoviral vector-based vaccines showed 70% and 85% efficacy, respectively, against Omicron BA.1 variants in the absence of Omicron-specific nAbs. is related to Therefore, other immune responses besides nAbs play an important role in providing protection against severe COVID-19.

Virus-specific CD8+ T cells can detect and eliminate infected cells, but their direct function in vaccine protection against COVID-19 remains to be determined. To date, all phase III clinical trials of COVID-19 vaccines have excluded evaluation of cell-mediated immune responses as an immune correlate.recently scientific immunology In a study, scientists are evaluating the role of CD8+ T cells in vaccine protection against SARS-CoV-2 infection in rhesus monkeys.

About research

A total of 30 adult male and female rhesus monkeys were assigned to six groups.All animals were immunized with her 5×10^Ten Johnson & Johnson Ad26.COV2.S adenoviral vector-based vaccine viral particles. This is equivalent to the human dose of the vaccine.

All test rhesus monkeys were immunized via the intramuscular route at week 0. Test animals were subsequently injected with a CD8-depleting monoclonal antibody (mAb) at week 5, followed by a Delta variant challenge at week 6.

Each group received 50 mg/kg of anti-CD8β CDR-grafted rhesus monkey immunoglobulin G1 (IgG1) antibody (CD8b255R1), anti-CD8α CDR-grafted rhesus monkey IgG1 antibody (MT807R1), or an isotype-matched control antibody.

Survey results

Vaccination with Ad26.COV2.S elicited CD8+ T cells that significantly contributed to the control of SARS-CoV-2 upon high-dose heterologous challenge with the rhesus Delta variant.

Immune response after vaccination. Antibody responses at 0, 4, and 6 weeks after vaccination and challenge with Ad26.COV2.S. a, Neutralizing antibody (NAb) titers by luciferase-based pseudovirus neutralization assay. B.Receptor binding domain (RBD)-specific binding antibody titers by ELISA. Hapooled peptide spike-specific IFN-γ CD8⁺ and CD4⁺ T cell responses by intracellular cytokine staining assay two weeks after vaccination with Ad26.COV2.S. Responses were measured against SARS-CoV-2 WA1/2020 (black), B.1.617.2 (Delta; blue), and B.1.1.529 (Omicron; green) variants. The dotted line represents the limit of quantitation. Median values ​​(red bars) are shown.

In vaccinated animals, depletion of CD8+ T cells resulted in viral load in the upper and lower respiratory tract after inoculation of animals with the delta mutant. Depletion of CD8α had a significant impact on viral load, possibly due to the functional role of natural killer (NK) cells or depletion of CD8 by anti-CD8α mAbs.

Previous observations that the BNT162b2 and Ad26.COV2.S vaccines provided significant protection against severe infection with the Omicron BA.1 variant in the absence of the Omicron-specific nAbs are supported by the current study as well. reported. Previous studies have also shown that, unlike nAb responses, T cell responses show higher cross-reactivity to SARS-CoV-2 variants, including Omicron BA.1. This is also supported by current research. These findings thus establish a definitive immunogenicity landscape for clinical observation.

Ad26.COV2.S vaccination induced CD8+ T cell responses and contributed to control viral load in SARS-CoV-2 challenged rhesus monkeys in a high-dose heterologous challenge model. Current models focused solely on virologic control in animals challenged with SARS-CoV-2 Delta variants. Therefore, we cannot use this animal model to determine the role of CD8+ T cell responses in providing protection during COVID-19.

A previous macaque model-based study reported that higher antibody titers can prevent SARS-CoV-2 infection. However, all currently available COVID-19 vaccines, even after booster vaccination, have shown modest and short-term efficacy in preventing individuals from becoming infected with the SARS-CoV-2 Omicron variant. I’m here.

Conclusion

In summary, this study highlighted the important contribution of CD8+ T-cell responses after vaccination with Ad26.COV2.S in providing protection against SARS-CoV-2 replication using the rhesus monkey model.

The authors speculated that CD8+ T cell responses also control viral load after mRNA vaccination. However, this observation requires further validation. Importantly, the CD8+ T cell response adequately limits SARS-CoV-2 variants such as the Delta and Omicron strains, which are known to partially evade the nAb response.

In the future, researchers will need to determine whether CD8+ T cell responses also have a positive impact on SARS-CoV-2 vaccine protection in humans. Therefore, further studies should also focus on her T-cell responses along with antibody titers to assess vaccine efficacy in humans.