Phase I/II trial findings support use of CoronaVac vaccine in older individuals

By Sally Robertson, B.Sc.Feb 4 2021

Researchers in China have reported phase I/II clinical trial findings showing that the vaccine candidate CoronaVac is well tolerated among older individuals and effectively generates antibody responses against severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) - the agent that causes coronavirus disease 2019 (COVID-19).

CoronaVac is an inactivated SARS-CoV-2 vaccine developed by Chinese pharmaceutical company Sinovac Life Sciences based in Beijing, China.

Writing in The Lancet Infectious Diseases, the team says this is the first report of an inactivated SARS-CoV-2 vaccine tested in older adults (aged 60 years or older). The findings support its use in this older population.

Weidong Yin from Sinovac Biotech and colleagues say all adverse reactions to the vaccine were mild or moderate in severity, with the most common one being pain at the injection site.

Further studies are now needed to test the effectiveness of Coronavac at preventing COVID-19 in older adults, says the team.

The study is ongoing and is registered with ClinicalTrials.gov (NCT04383574).

Study: Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Image Credit: NIAID

Older individuals are at increased risk of severe COVID-19 and death

Research has shown that individuals aged 60 or older are at an increased risk of severe illness and death from COVID-19, particularly if they have underlying health conditions.

A vaccine that protects older individuals against COVID-19 is therefore urgently needed.

However, the response to vaccination is often reduced among older adults due to age-related changes that affect both the innate and adaptive immune systems – a phenomenon called immunosenescence.

More about CoronaVac

“Purified inactivated viruses have traditionally been used for vaccine development, and currently eight inactivated COVID-19 candidate vaccines are in clinical evaluation,” says Yin and the team.

Although efficacy results are not yet available, studies have demonstrated that these vaccines induce neutralizing antibody responses against SARS-CoV-2 and have good safety profiles.

The researchers previously reported the results of a phase I/II clinical trial of CoronaVac in participants aged 18–59 years.

The results showed that CoronaVac was well tolerated and induced humoral responses against SARS-CoV-2. Seroconversion rates ranged from 92% to 100% after two doses of CoronaVac (3 µg and 6 µg) administered 2 or 4 weeks apart.

What did the current study involve?

Now, the team has conducted a randomized, double-blind, placebo-controlled, phase I/II clinical trial to assess the safety, tolerability, and immunogenicity of CoronaVac in adults aged 60 years and older.

“This is the first report of an inactivated SARS-CoV-2 vaccine, CoronaVac, tested in older adults (aged 60 years or older),” writes Yin and colleagues.

Phase I involved 72 participants, aged a mean of 65·8 years, who were enrolled between May 22^nd and June 1^st, 2020. Phase II involved 350 participants, aged a mean of 66·6 years, enrolled between June 12^th and June 15^th, 2020.

For phase 1, a dose-escalation study was performed with participants randomly assigned to receive 3 µg or 6 µg doses of either CoronaVac or placebo 28 days apart.

For phase 2, participants were randomly assigned to receive 1·5μg, 3µg, or 6µg doses of CoronaVac or placebo 28 days apart.

The primary safety endpoint was adverse reactions within the 28 days following each injection. The primary immunogenicity endpoint was seroconversion rate 28 days following the second injection.

Seroconversion was defined as a change from seronegativity at baseline to seropositivity for neutralizing antibodies against live SARS-CoV-2. For those who were seropositive at baseline, seroconversion was defined as a four-fold increase in anti-SARS-CoV-2 neutralizing antibody titer.

What were the findings?

The researchers found that two shots of CoronaVac were safe and well-tolerated at doses of 1·5μg, 3μg, and 6μg among adults aged 60 years and older.

“The results were similar to our study of adults aged 18–59 years,” says the team.

Across both phases, adverse reactions within 28 days of injection occurred at a rate of 20% in the 1·5μg group, 20% in the 3μg group, 22% in the 6μg group, and 21% in the placebo group.

“The incidence of adverse reactions in different dose groups was similar, indicating that there was no dose-related aggravation concern with regard to safety,” writes Yin and colleagues.

Moreover, all adverse reactions were mild or moderate in severity and pain at the injection site was the most commonly reported (9%) event.

The researchers say, “CoronaVac is safe and well-tolerated in older adults.”

What about immunogenicity?

In phase I, seroconversion was observed in 24 of 24 (100%) participants in the 3μg group and in 22 of 23 (95·7%) participants in the 6μg group.

In phase 2, seroconversion was observed in 88 of 97 (90.7%) participants in the 1·5μg group, 96 of 98 (98.0%) in the 3μg group, and 97 of 98 (99·0%) participants in the 6μg group.

“Among the three doses evaluated, the neutralizing antibody titers induced by the 3μg dose were similar to those of the 6μg dose and higher than those of the 1·5μg dose,” writes Yin and colleagues.

“Combined with the safety and production capacity, the 3μg dose of CoronaVac with a two-dose immunization schedule is being used in the ongoing phase 3 trials to assess protection against COVID-19,” says the team.