The phase 1/2 findings show the recently regulated two-dose vaccine was associated with no serious adverse events and antibody response within 21 days.
New non-randomized phase 1/2 data from the Russia-regulated vaccine for coronavirus 2019 (COVID-19) showed the two-part recombinant human adenovirus type 26 and type 5 (rAd26-S; rAd5-S) prophylaxis was not associated with any serious adverse events and elicited antibody response over 42 days.
The pair of 38-patient trials, conducted from June-August this year, assessed a frozen and freeze-dried formulation of the vaccine for its safety, then immune response, in healthy adult participants.
Led by Dr. Denis Y. Logunov, of the NF Gamaleya National Research Center for Epidemiology and Microbiology in Moscow, investigators conducted the pair of open, non-randomized phase 1/2 trials at 2 different hospitals in Russia. In aiming to assess the safety and immunogenicity of the frozen and lyophilized formulations of the vaccine, they enrolled healthy adult volunteers aged 18-60 years old.
One-dose intramuscular injections of either rAd26-S or rAd5-S were administered at baseline, with safety of both components assessed for 28 days. Safety outcomes included total participants with adverse events monitored throughout the trial.
In phase 2—designated to begin at ≥5 days after the phase 1 initiation—investigators administered the booster vaccination, seeking a primary outcome of antigen-specific humoral immunity as per SARS-CoV-2-specific antibodies measured by enzyme-linked immunosorbent assay (ELISA) on days 0, 14, 21, 28, and 42.
Logunov and colleagues sought secondary outcomes including antigen-specific cellular immunity and change in neutralizing antibodies, as per a SARS-CoV-2 neutralization assay.
Through both trials, 9 each (18 total) received rAds26-S and rAD5-S in phase 1, and 20 received rAds26-S and rAD5-S in phase 2.
The team observed generally safe and tolerable outcomes, with the most common adverse events including injection site pain (58%), hyperthermia (50%), headaches (42%), asthenia (28%), and muscle/joint pain (24%). Among all observed adverse events, none were considered serious in severity.
All participants produced antibodies to SARS-CoV-2 glycoprotein, with receptor-binding domain-specific IgG titers tallying 14,703 with frozen vaccine formulation and 11,143 lyophilized vaccine formulation.
Neutralizing antibodies were 49.25 and 45.95 with each formulation, respectively, with a seroconversion rate of 100%. All participants had cell-mediated responses at day 28. Median cell proliferation was 2.5% CD4 and 1.3% CD8 with the frozen formulation, and median cell proliferation of 1.3% CD4 and 1.1% CD8 with the lyophilized formulation.
In a statement accompanying the new data release, Logunov emphasized the utility of booster vaccination with a different adenovirus vector. He stressed the importance, overall, of providing a booster vaccination for any SARS-CoV-2 candidate—a practice which has been almost entirely uniform among the leading potential vaccines in research now.
“However, booster vaccinations that use the same adenovirus vector might not produce an effective response, because the immune system may recognize and attack the vector,” Logunov said. “This would block the vaccine from entering people’s cells and teaching the body to recognize and attack SARS-CoV-2. For our vaccine, we use two different adenovirus vectors in a bid to avoid the immune system becoming immune to the vector.”
In a commentary accompanying the study, Naor Bar-Zeev, PhD, MPH, of the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health, described the Russia findings as “encouraging but small.” He cited the immunogenicity results as lacking specific outcomes for older age groups—a notably at-risk population for COVID-19 severity and mortality—and like other currently assessed candidates, the Russia vaccine lacks clinical efficacy data for COVID-19 itself.
“Licensure in most settings should depend on proven short-term and long-term efficacy against disease (not just immunogenicity) and more complete safety data,” Bar-Zeev wrote. “Safety assurance will then require further large-scale surveillance after licensure. Such surveillance is not well established in many settings, and rapid efforts need to be made by governments, regulators, and global research funders to get those systems in place.”
In the next steps of assessment, the Russia investigators will conduct a large-scale trial in a participant general population in the context of a phase 3 study. Such a study was approved on August 26, and will include 40,000 volunteers from differing age and risk groups, and will include constant patient status monitoring through an online application.