Researchers said factors such as testing and lab methods made it difficult to directly compare the CoronaVac results with those of other vaccines

There are signs that immune protection from the world’s most widely used coronavirus vaccine drops significantly after six to eight months but a booster shot lifts levels three to five times, a new study has found.

The study came as some countries, including Thailand, Indonesia and Turkey, consider offering a third booster shot to people in high-risk and older age groups. The study was published on Medrxiv.org without peer review on Sunday.

Since May last year researchers, including Yu Hongjie with Fudan University’s school of public health, and Zhu Fengcai, deputy director of Jiangsu Centre for Disease Control and Prevention, have tested the immunogenicity – the ability of cells or tissues to provoke an immune response – of Sinovac’s CoronaVac vaccine, of which 3.73 billion doses have been administered worldwide. It is one of the two vaccines rolled out in Hong Kong.
They are investigating how long CoronaVac induces immunity, whether a booster shot will be needed and, if so, the optimal timing of the booster.

Participants were randomly assigned to groups and administered two doses either 14 days or 28 days apart. Each group was either administered a 3 microgram dose, a higher 6 microgram dose or a placebo. Four weeks later, higher concentrations of antibodies were found among those who been vaccinated with a longer spacing between doses.

But six to eight months later, the concentration of neutralising antibodies – an indicator of immunity induced by the vaccines – of all the two-dose participants declined to below the “seropositive cut-off” set by researchers, according to the paper.

About 540 participants received a third shot at different intervals – after 42 days, 56 days, 194 days or 208 days – to find out the best regimen for the booster shot. For short intervals of a third shot – 42 days and 56 days after the second dose – the level of neutralising antibodies rose slightly or moderately, according to tests 28 days after the third shot, and they dropped to almost the seropositive cut-off threshold six months later.

Those vaccinated with the third shot with a much longer interval – six to eight months – had a level of neutralising antibodies three times to four times that of the short-paced vaccines, with no significant difference between the dosage groups.

“Our results demonstrated that two doses of CoronaVac induce good immunogenicity. Although neutralising antibody levels declined to near positive cut-off titre of 8 after six months, a two-dose vaccination schedule generated good immune memory,” the researchers wrote.

“A third dose, given at an interval of six-eight months after the second dose, led to a strong boost in immune response … an increase corresponds to three-five fold increase in neutralising antibody titres 28 days after the second dose, indicating an anamnestic memory B cell response.”

Researchers did not directly propose when a third dose of the CoronaVac would be suitable, but said the timing of a booster dose must take into account the local epidemic situation, the risk of infection and vaccine supply as well as other factors.

Zhuang Shilihe, a Guangzhou-based vaccine expert, said although it remained unclear how much protection neutralising antibodies in the serapositive cut-off level set in the study would offer, the level of antibody after six to eight months was “very low” – an expected result because of the limitations of inactivated vaccines.

Even though the vaccine could induce “memory B cell response”, it was still preferred to induce higher levels of neutralising antibodies for immediate protection.

“It takes time to mount the immune response by memory B cells. You might be killed before your immunity kills the virus,” Zhuang said. “That’s why it’s important to have high levels of neutralising antibodies to prevent becoming sick, severely ill or dying.”

He said it would take time to see how the level of neutralising antibodies dropped six months after the longer-interval booster shot, but he expected it to be higher than the shorter-interval booster shot.
Researchers said it was difficult to directly compare the estimates in the findings with those of other vaccines such as Moderna and AstraZeneca because of different testing methods, a lack of standardised laboratory methods for coronavirus neutralisation and other issues.

The study was conducted among healthy adults 18 to 59 years old and did not include those of higher risk of severe outcomes from the virus and nor did it assess rare vaccine side effects.

In Preprints with The Lancet, another article showed that 623 adverse events were recorded from the 7.12 million doses of Covid-19 vaccines administered – including 608 million doses of CoronaVac – in the northern Chinese city of Dalian from November to June.

More than 87.3 per cent of those were confirmed as common minor vaccine reactions. There were five cases of very rare anaphylaxis after vaccination (0.7 per 1 million doses). Seven negative reactions were classified as serious but a causal relationship with vaccination was ruled out.

The severe adverse events following immunisation were lower than overall severe adverse event rates from non Covid-19 vaccinations of the past, wrote the researchers from Fudan University and the Dalian Centre for Disease Control and Prevention.

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