On Feb 27th, 2021, the FDA issued emergency use authorization for a third COVID vaccine in the U.S., the Johnson & Johnson Janssen vaccine. The FDA Vaccine Advisory Panel reviewed the vaccine during their meeting on Feb 26th and recommended authorization based on material submitted by the manufacturer and the FDA’s independent review of the study data. The vaccine, labeled Ad26.COV2.S, is a “replication-incompetent adenovirus type 26 (Ad26) vectored vaccine encoding a stabilized variant of the SARS-CoV-2 S protein”. If you are not familiar with adenovirus vaccines, the CDC has a good explanation on their website.
The vaccine was studied in adults, age 18 and over, as a single 0.5ml intramuscular injection containing 5×1010 viral particles. The Phase 3 trial included 40,000 participants with results reported in two groups, 14 and 28 days after vaccination. Symptoms were also classified into moderate and sever illness. The submitted trial data was collected over 2 months and concluded on January 22nd, 2021. However, post trial monitoring and data analysis is still ongoing.
The trial utilized the following criteria for severe illness: A positive PCR or molecular test AND any one of the following
- Clinical signs at rest indicative of severe systemic illness:
- Respiratory rate ≥30 breaths/minute
- Heart rate ≥125 beats/minute
- Oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg
- Respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO])
- Evidence of shock (defined as systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, or requiring vasopressors)
- Significant acute renal, hepatic, or neurologic dysfunction
- Admission to the ICU
The trial findings are summarized in the table below. Overall efficacy was determined to be 66% against moderate or severe illness, in all geographic regions participating in the trial. Efficacy specifically against severe cases was better, and there were no COVID related deaths in the vaccine group.
|Vaccine > 14 days||Vaccine > 28 days||Placebo > 14 days||Placebo > 28 days|
|Efficacy vs mod-sev COVID||66.9%||66.1%||–||–|
|Efficacy vs severe COVID||76.7%||85.4%||–||–|
|Deaths due to COVID||0||0||2||5|
Unlike the Pfizer and Moderna trials, the Johnson & Johnsons trial occurred during a period when variants were known to be emerging. The following variants were sequenced from COVID cases that occurred during the trial:
- Wuhan-H1 variant D614G in the U.S. (96.4% of sequenced cases)
- 20H/501Y.V2 variant (B.1.351) in South Africa (94.5% of sequenced cases)
- P.2 lineage in Brazil (69.4% of sequenced cases, with the remaining 30.6% Wuhan-H1 variant D614G)
- No cases identified of B.1.1.7 (U.K) or P1 (Brazil) lineages as of February 12, 2021
Analysis of all COVID positive samples in the trial is still ongoing so the FDA reviewers noted that it is too early to determine specific variant efficacy. As of Feb 12th, 2021, the trial data included the following viral sequencing completion rates and country specific efficacy:
- United States
- 73.5% sequencing complete
- 28 day efficacy 72% against moderate and 85.9% against severe COVID illness.
- South Africa
- 66.9% sequencing complete
- 28 day efficacy 64% against moderate and 81.7% against severe COVID illness.
- 69.3% sequencing complete
- 28 day efficacy 68.1% against moderate and 87.6% against severe COVID illness.
Much like previous COVID vaccines, most side effects were mild. The most commonly reported were:
- Injection site pain (48.6%),
- Headache (38.9%)
- Fatigue (38.2%)
- Myalgia (33.2%);
- Side effects were less likely in those > 60 yo
Serious adverse reactions included:
- One serious hypersensitivity reaction, reported 2 days post vaccination.
- One case of Guillain-Barre Syndrome in each of the vaccine and placebo groups. The vaccine group case but was still classified by the FDA as possibly related to vaccination.
- One case of pericarditis, thought to be possibly related to vaccination.
- One cases of bell’s palsy occurred in each of the vaccine and placebo groups. Both were felt to be unrelated.
“Numerical Imbalance” was reported for several conditions with insufficient data to determine a causal relationship to the vaccine. These cases represent conditions that occurred more frequently in the vaccine group but for unclear reasons and without reaching statistical significance.
- Non-serious urticaria events, 5 vaccine group vs 1 placebo
- Thromboembolic events (DVT and PE), 15 vaccine group vs 10 placebo
- Tinnitus, 6 vaccine group vs 0 placebo
Deaths were reported in 3 vaccinate recipients and 16 placebo recipients. In the vaccine group, none were believed to be related to vaccination with causes of death given as lung abscess, non-COVID pneumonia, and unknown. In the placebo group, 6 deaths were confirmed due to COVID and one probable COVID (per FDA review) for a total of 7 COVID related deaths.
|Age > 60 yo||7331||7341|
|Female||9820 (44.9%)||9902 (45.2%)|
|Male||12071 (55.1%)||11982 (54.7%)|
|American Indian or Alaska|
|2083 (9.5%)||2060 (9.4%)|
|Asian||743 (3.4%)||687 (3.1%)|
|Black or African American||4251 (19.4%)||4264 (19.5%)|
|Native Hawaiian or other Pacific Islander||58 (0.3%)||48 (0.2%)|
|White||12858 (58.7%)||12838 (58.7%)|
|Hispanic or Latino||9874 (45.1%)||9963 (45.5%)|
Countries included in the phase 3 trial:
- Argentina 2996 (6.8%)
- Brazil 7278 (16.6%)
- Chile 1133 (2.6%)
- Colombia 4248 (9.7%)
- Mexico 479 (1.1%)
- Peru 1771 (4.0%)
- United States 19302 (44.1%)
- South Africa 6576 (15.0%)
The FDA compiled the table below from the study data demonstrating the various comorbidities represented in the vaccine and placebo groups. In addition, 9.6% of vaccinated participants in the study had evidence of previous infection with SARS-CoV-2 at baseline, as assessed by serology (antibody) testing prior to vaccination.
The FDA provided the graph below detailing the point at which COVID cases diverge between the two groups. It demonstrates the beginning of immunity on day 14 post vaccination with continued lower numbers of cases in the vaccine group (blue line) versus the placebo group (red line) as time goes on.
Two additional J&J Janssen studies are ongoing:
- A phase 3 study investigating the efficacy and safety of a 2 dose regimen in 30,000 adults (enrollment ongoing).
- A phase 2a study investigating the safety and immunogenicity of 1 and 2 dose regimens using multiple strengths in 550 adults 660 adolescents 1-dose and 2-dose regimens (enrollment of adults ongoing; enrollment of adolescents not started).
- 1×1011 viral particles, 5×1010 viral particles, 2.5×1010 viral particles, 1.25×1010 viral particles
Overall, the Johnson & Johnson Janssen COVID vaccine accomplishes what we want it to. There were no hospitalizations 28 days after vaccination (and only 2 sooner), plus there were no deaths. That is an incredible accomplishment. The vaccine was tested in a wide group of patients with numerous medical conditions and demonstrated sufficient efficacy to prevent a majority of moderate cases of infection and even more of the serious infections. Furthermore, it is a single dose vaccine with only simple refrigeration required for storage. These qualities make it an excellent addition to the armamentarium against COVID-19.