A recent study from Thailand, published in the journal Lancet Infectious Diseases, highlights a rather low degree of neutralization-afforded protection mounted by the inactivated whole-virus CoronaVac vaccine compared to natural infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the virus that causes coronavirus disease 2019 (COVID-19).

Vaccines against COVID-19 are indispensable in our pandemic response, as they offer protection against severe clinical presentations and death. Furthermore, raising vaccination rates will be pivotal in our return to prepandemic normalcy.

Still, the real-world effectiveness of various vaccines may vary in different countries due to the emergence and spread of new variants. Although we have data from several countries for Pfizer/BioNTech and Moderna mRNA vaccines, as well as Oxford-for AstraZeneca vaccine, data from countries that use inactivated whole-virus CoronaVac vaccine and that have a surge in SARS-CoV-2 viral variants are lacking.

The aforementioned CoronaVac vaccine (Sinovac Biotech, Beijing, China) has been approved for emergency use in mass vaccination programs in many low-income countries, and the literature shows 87.5% vaccine effectiveness against hospitalization and 86.3% vaccine effectiveness against fatal outcomes.

But in Thailand, there is a co-circulation of several SARS-CoV-2 variants of concern, which includes alpha (B.1.1.7), beta (B.1.351) and delta (B.1.617.2) variants. And since CoronaVac was used for mass vaccination in this country, the question remains whether the protective and neutralization effect is adequate to tackle the ongoing spread of the disease.

Quantifying antibodies in two groups of patients

In this study, first-authored by Dr. Vimvara Vacharathit from the Mahidol University in Bangkok (Thailand), the aim was to appraise the impact of SARS-CoV-2 variants of concern on both vaccine-induced and infection-induced protective antibodies.

For that purpose, this research group has evaluated titers of SARS-CoV-2 IgG antibodies that bind to the receptor-binding domain (RBD) of the virus, as well as neutralizing antibody titers against both SARS-CoV-2 prototypic vaccine strain (also known as the wild-type virus) and variants of concern. They have used sera of healthcare workers who had received two doses of the vaccine.

Then they have compared the results with sera from naturally infected patients who were not vaccinated and who had been hospitalized in the period between March and May, 2020, but also in the period between April and May, 2021. A live-virus micro-neutralization assay has been used for neutralizing antibody titer quantification.

How effective is CoronaVac vaccine?

The researchers have found that wild-type virus was best neutralized by sera from natural infection in 2020, while the alpha variant was best neutralized by sera from natural infection in 2021. Equal neutralization properties of sera from these two periods have been observed for the beta variant, and the same was valid for the delta variant (albeit with lower titers).

Even though there was a sturdy production by RBD-binding IgG and 100% of participants in all cohorts had virus-specific antibodies, neutralization properties have been markedly reduced (and sometimes even undetectable) against the three variants of concern in comparison with the wild-type virus in sera from all the tested groups.

Moreover, the potency of neutralizing antibodies against alpha and beta variants of concern is actually comparable in sera of CoronaVac vaccinees, which is actually in opposition to previous scientific reports showing that the beta variant is much more resistant to neutralization than the alpha variant.

The problem is that the most transmissible and currently most dominant delta variant – which also possibly belongs among the most virulent of variants of concern that have been identified to date – appears to be most resistant to neutralization.

Towards an optimal mitigation strategy

Although titers of neutralizing antibodies do not represent an exclusive immune correlate of protection, we can actually consider them highly predictive of immune defense from symptomatic SARS-CoV-2 infection.

Our study highlights a low degree of neutralization-afforded protection mounted by CoronaVac when compared with natural infection,” emphasize study authors in this publication. “Further booster doses, heterologous or otherwise, beyond the conventional two-dose regimen might be needed for recipients of CoronaVac to maintain a long-term anamnestic response,” they add.

In conclusion, considering a steady decay of neutralizing antibodies over time, as well as the continued appearance of divergent SARS-CoV-2 variants, it is of utmost importance to maintain effective mitigation strategies and to carry on with vaccine efficiency monitoring – especially in countries and/or regions with circulating SARS-CoV-2 variants of concern.

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.