Early Data Shows Promise for Johnson & Johnson’s COVID-19 Vaccine

September 30, 2020 - Johnson & Johnson recently announced early positive results from the ongoing Phase 1/2a clinical trial of its COVID-19 vaccine candidate.

The results published in medRxiv, a preprint server for health services run by Cold Spring Harbor Laborotory, BMJ, and Yale, showed that a single dose of the Ad26.COV2.S, which is also known as JNJ-78436735, induced a strong neutralizing antibody response and was well tolerated in almost all participants aged 18 years and older.

However, the results from the clinical trial have not been peer-reviewed, nor have they been published in the medical, clinical, and related health services.

The multi-center Phase 1/2a clinical trial was randomized and double-blinded. It assigned 405 eligible participants aged 18 to 55 years and 405 participants younger than 65 years.

Researchers administered either a dose level of 5x10 or 1x10 viral particles per vaccination, either as a single dose or as a two-dose schedule. The doses were spaced eight weeks apart.

Johnson & Johnson recently announced the launch of a large-scale, multi-country Phase 3 clinical trial for the vaccine candidate. 

The ENSEMBLE trial will enroll nearly 60,000 volunteers across three continents and will study the safety and efficiency of a single dose of Ad26.COV2.S versus a placebo.

The study will include both individuals with and without comorbidities associated with greater risk of progression to severe COVID-19.  

“We did observe a trend for higher reactogenicity with the higher vaccine dose,” researchers said in the pre-print paper. “More details on the safety and reactogenicity profile will be provided immediately upon group unblinding of the study, after vaccine dosing in cohort 1a and 3 has been completed.”  

Researchers reported interim results after the first dose of safety data from Cohorts 1a, 1b, and 3, and group immunogenicity data from Cohorts 1a and 3.

Local adverse events were reported in 58 percent of Cohort 1 participants and 27 percent of Cohort 3 participants, researchers said. Solicited systemic adverse events were also reported in 64 percent of Cohort 1 participants and 36 percent of Cohort 3 participants. 

Additionally, S-binding antibody titers increased from baseline to Day 29 post-vaccination in 99 percent of the participants in Cohort 1a and 100 percent of the participants in Cohort 3.

While neutralizing antibody responses in all participants receiving Johnson & Johnson’s vaccine candidate were reported after a single dose, all other COVID-19 vaccines currently in clinical development require two doses.

“Several vaccine candidates are currently in different stages of development,” researchers said. 

“We have developed Ad26.COV2.S, that is based on Janssen’s replication incompetent adenovirus serotype (Ad26) vector, and a stabilized SARS-CoV-2 Spike (S) protein. This candidate was selected based on its immunogenicity and manufacturability profile.”

This positive data posted in medRxiv was consistent with preclinical studies, published in the scientific journal Nature. 

The data showed that Ad26-S.PP had an immune response among rhesus macaques as demonstrated by neutralizing antibodies. This prevented future infection and provided complete protection in the lungs among non-human primates.

Specifically, out of seven vaccine prototypes tested in the study, Ad26.COV2.S showed the highest levels of neutralizing antibodies to SARS-CoV-2. 

There were also receptor binding domain (RBD)-specific binding antibodies in 31 of 32 vaccinated animals by the second week of the study and in all vaccinated animals by the fourth week. Robust neutralizing antibodies responses were also found after a single immunization, which provided complete protection against SARS-CoV-2 in five of six animals. 

“A single-shot SARS-CoV-2 vaccine would have important logistic and practical advantages compared with a two-dose vaccine for mass vaccination campaigns and pandemic control. However, we would expect that a two-dose vaccine with Ad26-S.PP would be more immunogenic,” researchers said in the study.

And Dan Barouch, MD, PhD, director of the center for virology and vaccine research at BIDMC and the Ragon Institute, noted that the pre-clinical data suggests that antibody levels may serve as a biomarker for vaccine-medicated protection.