Single-Shot Johnson & Johnson Vaccine Demonstrates Robust Protection Against Multiple SARS-CoV-2 Variants, According to Studies in Nature and NEJM

Today, a paper published in *Nature* details the latest progress on a COVID-19 vaccine. The research reveals that this vaccine generates multiple protective mechanisms: even if the protective efficacy of one component declines against SARS-CoV-2 variants, the remaining mechanisms can still exert their effects! More importantly, this vaccine has already been validated in real-world settings. A single dose is sufficient to confer protective efficacy against multiple SARS-CoV-2 variants.

This vaccine was developed by Johnson & Johnson and received emergency use authorization from the U.S. FDA several months ago. To better understand the immunogenicity of this vaccine, researchers administered it to 20 volunteers. Subsequently, they analyzed the protective efficacy induced by the vaccine in the volunteers across multiple dimensions.

First is the level of neutralizing antibodies generated by the vaccine. Scientists found that, compared to the early SARS-CoV-2 strains (unmutated), the neutralizing antibody titers induced by this vaccine decreased when tested against the Beta variant (first identified in South Africa) and the Gamma variant (first identified in Brazil), with reductions of 5.0-fold and 3.3-fold, respectively. This finding is consistent with previous research indicating that viral variants can negatively impact the protective efficacy of neutralizing antibodies.

However, beyond neutralizing antibodies, non-neutralizing antibody responses and T-cell responses are largely unaffected by viral variants. Researchers noted that even against the Beta variant, antibody-dependent cellular phagocytosis, complement deposition, and NK cell activation in volunteers remained largely preserved.

Furthermore, whether against wild-type SARS-CoV-2 or the Alpha (first identified in the UK), Beta, and Gamma variants, the CD8+ and CD4+ T cell responses in the volunteers remained at comparable levels. This also suggests that, beyond neutralizing antibodies, T cell responses in the human body may have maintained a critical baseline of antiviral defense.

Some may ask whether these findings are truly meaningful. In real-world settings, do immune responses beyond neutralizing antibodies also confer sufficient protection to vaccine recipients? A paper published earlier this year in *The New England Journal of Medicine* answered this question. In a Phase 3 clinical trial, nearly 20,000 participants received a single-dose vaccine, while approximately 20,000 others were administered a placebo.

The results demonstrated that the vaccine group significantly outperformed the placebo control group. Among the vaccinated cohort, there were fewer cases of moderate to severe and critical COVID-19, as well as fewer hospitalizations and deaths. Regarding safety, vaccine recipients more frequently experienced injection site pain, headache, fatigue, myalgia, and nausea. Most of these symptoms were mild to moderate in severity and lasted only 1 to 2 days.

The conclusion of the paper indicates that Johnson & Johnson's single-dose vaccine demonstrated safety and efficacy against symptomatic COVID-19.

▲ Mechanism of Action of This Vaccine (Image Source: Reference [2])

A press release from Harvard University today stated that, based on the protective efficacy observed in the Phase 3 clinical trial, the non-neutralizing antibody responses and T-cell responses demonstrated in the *Nature* paper may have played a protective role against COVID-19. Given that this Phase 3 clinical trial enrolled a substantial number of volunteers in South Africa, Brazil, and other regions, the significance of this finding is particularly noteworthy.

“The current vaccines were designed against the original SARS-CoV-2 strain at the onset of the pandemic. Whether SARS-CoV-2 variants will reduce the efficacy of these vaccines is a cause for concern,” said Dan H. Barouch, corresponding author of the *Nature* paper and professor at Harvard Medical School. “Although the mechanism of protection against COVID-19 remains unclear, the strong protective efficacy of this vaccine in these regions increases the likelihood of the view that ‘non-neutralizing antibody responses and/or T cell responses may confer protection.’ Another possibility is that even low levels of neutralizing antibodies are sufficient to provide protection against COVID-19.”

Note: The original text has been abridged.

References:

[1] Alter, G., Yu, J., Liu, J. et al. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature (2021). https://doi.org/10.1038/s41586-021-03681-2

[2] Jerald Sadoff et al., (2021), Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19, NEJM, DOI: 10.1056/NEJMoa2101544

[3] Single-shot COVID-19 vaccine generates robust immune responses against variants, Retrieved June 9, 2021, from https://news.harvard.edu/gazette/story/2021/06/single-shot-covid-19-vaccine-effective-against-variants/