Johnson & Johnson’s Ad26.COV2.S COVID-19 Vaccine Shows Durable Immune Response After Single Dose in Phase 1/2a Trial

Among the investigational COVID-19 vaccines that have entered Phase 3 clinical development, Ad26.COV2.S, a candidate vaccine developed by Johnson & Johnson, is one of the few planned for single-dose administration to prevent COVID-19. Recently, the latest results from its Phase 1/2a clinical trial were published in The New England Journal of Medicine. The trial results showed that after a single dose of the Ad26.COV2.S vaccine, the vast majority of participants developed neutralizing antibodies against SARS-CoV-2, and antibody levels remained stable at 71 days post-vaccination.

Ad26.COV2.S uses the adenovirus vector Ad26 to express the full-length spike protein of SARS-CoV-2. Animal studies have shown that a single dose of this vaccine can achieve nearly complete protection. Another advantage of this investigational vaccine is its ability to be stored long-term at -4°C and remain stable for three months at 2–8°C. Therefore, if a single dose can provide robust protection against COVID-19, it would offer a convenient vaccine option.

A Single Dose Elicits a Durable Antibody Immune Response

In this trial, adult volunteers aged 18–55 years and elderly volunteers aged ≥65 years received different doses of Ad26.COV2.S or placebo, respectively.

The trial results showed that 29 days after the first dose, 99% and 96% of participants in the adult groups receiving low-dose and high-dose vaccines, respectively, achieved neutralizing antibody seroconversion (neutralizing antibody levels met the positivity criteria). Moreover, neutralizing antibody titers remained stable during subsequent follow-up; by day 71 after the first dose, not only did the neutralizing antibody titers remain stable, but 100% of vaccinees achieved neutralizing antibody seroconversion. These findings demonstrate the durability of the antibody immune response elicited by Ad26.COV2.S.

Participants aged 65 years and older achieved neutralizing antibody seroconversion rates of 96% (low dose) and 88% (high dose), respectively, at 29 days after the first vaccination.

One concern regarding adenovirus-based COVID-19 vaccines is whether pre-existing neutralizing antibodies against adenoviruses in the human body may affect vaccine efficacy. Researchers found that neither the baseline levels of Ad26-specific neutralizing antibodies prior to vaccination nor the levels of Ad26-specific neutralizing antibodies generated after the first dose were correlated with SARS-CoV-2 neutralizing antibody levels.

Vaccine-Induced Cellular Immune Responses Help Enhance Protective Efficacy

In addition to neutralizing antibody responses, T-cell responses of the immune system also play an important role in providing protection against COVID-19. In this trial, regardless of whether it was the adult group or the elderly group, most participants (60%-83%) developed a Th1-biased CD4-positive T-cell response 15 days after the first vaccination.

In the adult group, 51%–60% of participants simultaneously generated CD8+ T-cell responses against the spike protein, an immune response that helps eliminate cells infected with SARS-CoV-2. The proportion of individuals generating CD8+ T-cell responses was relatively lower in the elderly group (24%–36%).

During the discussion session, researchers pointed out that a robust CD4+ Th1 immune response, combined with CD8+ T cell and antibody responses, would minimize the theoretical risk of vaccine-associated enhanced respiratory disease.

Currently, the Phase 3 clinical trial evaluating the protective efficacy of this investigational vaccine is expected to yield interim efficacy results in late January to early February. In an interview, Dr. Paul Stoffels, Chief Scientific Officer of Johnson & Johnson, stated that these results further strengthen confidence in the favorable efficacy of Ad26.COV2.S observed in the Phase 3 clinical trial.

Note: This article is intended to introduce medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a licensed healthcare provider at a reputable hospital.

References:

[1] Sadoff et al., (2021). Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine. NEJM, DOI: 10.1056/NEJMoa2034201.

[2] J&J’s one-shot Covid vaccine is safe and generates promising immune response in early trial. Retrieved January 14, 2021, from https://www.cnbc.com/2021/01/13/covid-vaccine-johnson-johnson-one-shot-safe-generates-immune-response.html

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