Johnson & Johnson's Single-Dose Ad26.COV2.S Vaccine Demonstrates Near-Complete Protection in Preclinical Studies

Today, Johnson & Johnson announced that its lead COVID-19 vaccine candidate has achieved positive results in preclinical studies. This investigational vaccine, based on the company’s Ad26 adenoviral vector, requires only a single dose. It not only elicited potent neutralizing antibody and cellular immune responses in non-human primate models, but also provided complete or nearly complete protection in subsequent challenge studies in animals. The study was published in Nature as an accelerated article preview. Based on these data, phase 1/2 clinical trials of the investigational vaccine Ad26.COV2.S have been initiated.

In this study, Johnson & Johnson researchers utilized the Ad26 adenoviral vector to express seven different SARS-CoV-2 spike proteins. The spike proteins underwent various modifications; some enhancements increased the expression levels of the spike protein, while others improved its stability, thereby more effectively eliciting immune responses in animals. Johnson & Johnson has previously developed multiple viral vaccines using its Ad26 adenoviral vector technology platform. Earlier this month, an Ebola virus vaccine developed using the same Ad26 adenoviral vector and manufacturing process received marketing authorization from the European Commission, demonstrating the safety and immunogenicity of this vaccine technology.

Researchers vaccinated a total of 52 rhesus macaques with COVID-19 candidate vaccines featuring different designs. They found that the candidate vaccine named Ad26.COV2.S (referred to as Ad26-S.PP in the Nature paper) elicited the strongest neutralizing antibody response. This candidate vaccine expresses the full-length transmembrane spike protein, incorporates mutations at the furin cleavage site, and includes two proline mutations to enhance stability.

▲Structural differences among seven candidate COVID-19 vaccines (Image source: Reference [2])

Using pseudovirus and live SARS-CoV-2 assays, the neutralizing antibody titers elicited by Ad26.COV2.S were fourfold higher than those observed in previously studied convalescent rhesus macaques and convalescent COVID-19 patients. Furthermore, Ad26.COV2.S was able to elicit spike protein-specific IgG and IgA antibody responses in bronchoalveolar lavage (BAL) samples.

Six weeks after vaccination, researchers challenged all animals with the virus. SARS-CoV-2 RNA was detected in bronchoalveolar lavage (BAL) fluid and nasal swab samples from all control animals. In contrast, among the six animals vaccinated with Ad26.COV2.S, no SARS-CoV-2 RNA was detected in BAL fluid samples from any of the animals, and very low levels of SARS-CoV-2 RNA were detected in nasal swab samples from only one animal. This indicates that this COVID-19 vaccine provides complete or nearly complete protection to the upper and lower respiratory tracts in animals.

▲ Candidate COVID-19 vaccine confers near-complete protection in animals (BAL: bronchoalveolar lavage; S.PP: animal group vaccinated with the candidate COVID-19 vaccine; image source: Reference [2])

References:

[1] Single Dose of Johnson & Johnson COVID-19 Vaccine Candidate Demonstrates Robust Protection in Pre-clinical Studies. Retrieved July 30, 2020, fromhttps://www.jnj.com/single-dose-of-johnson-johnson-covid-19-vaccine-candidate-demonstrates-robust-protection-in-pre-clinical-studies

[2] Mercado et al., (2020). Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature, https://doi.org/10.1038/s41586-020-2607-z

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