After Two Sinovac Doses, Should the Booster Be BioNTech or Sinovac?

A group of researchers at Dokuz Eylül University examined the question, "after two doses of Sinovac, should the booster coronavirus vaccine be BioNTech or Sinovac". They analyzed antibody levels after booster doses among healthcare workers in Turkey. The findings were presented at the 6th National Congress of Clinical Microbiology.

A Brief Review of Coronavirus Vaccination in Turkey

On 13 January 2021, emergency use approval was granted for Sinovac, an inactivated coronavirus vaccine, to be administered in Turkey. In line with international recommendations, healthcare workers and individuals in high-risk groups were to be vaccinated first.

On 1 July 2021, third-dose vaccination with Sinovac or BioNTech began for healthcare workers. Homologous (Sinovac after 2 Sinovac doses) / heterologous (BioNTech after 2 Sinovac doses) boosters were thus administered approximately 5 months after completion of the inactivated vaccine schedule.

Predicting Whether the Vaccine Has Taken Effect

Measuring neutralizing antibody levels strongly predicts immune protection against symptomatic coronavirus disease (symptomatic Covid-19) after vaccination, but is technically difficult in practice. Instead, immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of the spike protein can be used as a predictive tool when evaluating vaccine effectiveness.

The study evaluated, among healthcare workers at Dokuz Eylül University Hospital who had received two Sinovac doses, 3-month anti-RBD IgG seropositivity* rates and quantitative changes in antibody levels, along with the subsequent effects of heterologous (BioNTech) and homologous (Sinovac) booster doses.

*Note: Seropositivity is the presence of antibodies against a particular microorganism in an individual.

This study included 548 healthcare workers with a mean age of 38. Of them, 146 (26.6%) had at least one chronic condition, and 17 (3.1%) were receiving immunosuppressive (immune-suppressing) modulator treatment.

Study Results

After two Sinovac doses, high seropositivity (98.9%) was detected in the first month. Other Sinovac effectiveness studies reported rates ranging from 98.2% to 99.6%. However, this rate is greater than 99.5% for mRNA (BioNTech) and viral vector vaccines.

Factors such as nutrition, age and sex may affect vaccine effectiveness. Male sex, older age (>65 years), high body mass index (≥25 kg/m2), immunosuppressive treatment, cancer and kidney disease were identified as factors associated with a low immune response to Covid-19 vaccination. Booster doses are strongly recommended, especially for healthcare workers receiving immunosuppressive treatment, because other Sinovac studies have also produced similar results.

Obesity is also an important factor in vaccine effectiveness. Another study found higher BioNTech antibody levels in underweight and normal-weight individuals than in pre-obese individuals. In other words, obesity reduces vaccine effectiveness. 

When antibody levels at month four were compared with those in the first month, a decline of 61% and even a seronegativity rate of 10% were observed. Similarly, many studies have shown declining antibody levels after the first months following both Sinovac and BioNTech vaccination.

Should the Booster Be Sinovac or BioNTech?

Antibody levels increased in participants vaccinated again with Sinovac or BioNTech after 5 months (a booster dose). The results were consistent with the limited number of other studies examining booster effectiveness. The main question is which vaccine after two Sinovac doses – BioNTech or Sinovac – would contribute to higher antibody levels.

According to the study, antibody levels were significantly higher in people whose booster vaccine was BioNTech.

This study supports the limited number of studies comparing antibody responses after homologous or heterologous booster doses following two Sinovac vaccinations.  

In summary, the striking findings were;

1. Seropositivity was very high after two doses of inactivated Sinovac.
2. Having a chronic disease and being pre-obese caused a low antibody response.
3. Antibody levels declined substantially during the 4 months after the second Sinovac dose.
4. Both homologous and heterologous boosters approximately 5 months after the second Sinovac dose increased antibody levels.
5. The heterologous booster (BioNTech) produced a marked increase in antibody response compared with the homologous booster (Sinovac).

The researchers recommend that individuals who have completed the inactivated vaccine schedule, especially those with risk factors, choose an mRNA vaccine as their booster.