More evidence that mixing COVID-19 vaccines may help elicit a robust immune response

Eight volunteers who received a complete dose or a single dose of an mRNA vaccine or the ChAdOx1 vaccine after a dose of a trial gorilla adenovirus vaccine showed a significantly high level of antibodies and T cell response against SARS-CoV-2.

Although several vaccines have now been approved to combat the coronavirus disease (COVID-19) pandemic, several countries face shortages in vaccine supply. Most of the two-dose vaccines require that both doses be of the same vaccine. However, with these vaccine supply constraints, researchers have started evaluating the potential for mixing different types of vaccines.

Such mixing of vaccine types may not only help with vaccine availability constraints but also may be needed for long-term protection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, using a second dose of a different vaccine may help overcome vaccine hesitancy in people who have received a dose of the adenovirus-based vaccine, which had given rise to some safety concerns amid a number of cases of extremely rare blood clots.

Some countries in Europe, like Spain and Germany, are recommending a booster dose of an mRNA vaccine to people under 60 years who have received their first dose of Vaxzevria, made by AstraZeneca.

Mixing vaccine technologies

Heterologous vaccination, or vaccination doses using different vaccine technologies, has been known to improve immune response and has been proposed for other viruses and cancer. Vaccination data in mice provided evidence of the benefit of mixing vaccine technologies, and several clinical trials are underway to test the safety and efficacy of this strategy in COVID-19 vaccines.

Phase I clinical trials of a single dose regimen of a gorilla adenovirus-based vaccine, GRAd-COV2, showed it is both safe and induces good levels of binding and neutralizing antibodies.

At the end of 24 weeks of follow-up, eight volunteers reported that they had received either the full course or a single dose of the BNT162b2 mRNA vaccine or the ChAdOx1 vaccine as part of the Italian National Vaccination Campaign. This happened between 14 and 24 weeks of the GRAd-COV2 vaccination dose.

Researchers in Italy measured the immune response to this heterologous vaccination in these eight participants. They found that binding antibodies to the spike protein of SARS-CoV-2 increased significantly compared to the highest levels recorded at week 12. There was no difference between antibody levels of those who received two doses or a single dose of the different vaccines.

The researchers also measured the T cell response in the participants. The strong T cell response induced by GRAd-COV2 was increased further after vaccination with the mRNA or ChAdOx1 vaccine in five participants. The T cell response remained the same in the others.

Potential benefits

Although the number of participants in this study is very small and there is no safety data, the results suggest immune response after a single dose of GRAd-COV2 can be significantly boosted by a single dose of another vaccine technology.

Overall, these evidences support the concept that a single-dose of an adenoviral vaccine, which is cheap and easy to deploy in a pandemic setting, represents a good tool to effectively prime the immune system, which can be boosted afterwards by a single dose of a different vaccine platform, reaching high levels of immune responses,” write the authors.

Using adenovirus-based vaccines in the heterologous vaccination strategy may be important for inducing and continuing T cell response, which may provide cross-protection in the face of emerging SARS-CoV-2 variants. Further studies on safety and optimization of the timing of the doses of heterologous vaccination will help take forward this strategy.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).