5 Intriguing Things to Know About Mixing COVID-19 Vaccines

Thanks to global vaccination programs, healthcare providers have now administered nearly 12 billion doses of the COVID-19 vaccine. Some countries now follow a combined vaccine approach, where people receive an initial shot, followed by a booster of a different type. Experts call this heterologous prime-boost vaccination.

The policy of mixing different vaccines helps ensure that as many people as possible are protected against the disease by allowing for flexibility should one vaccine type become unavailable. It's also safe and effective.

Here are five things to know about the mixed-dose approach to COVID-19 vaccinations.

1. Combining vaccine types is a proven approach

The idea of combining vaccine types has been proven in different infectious diseases. HIV researchers in the 1990s combined vaccines because they believed that traditional vaccines couldn't induce the complex immunological response needed to protect the body against HIV infection. Because of the complicated nature of HIV infection, scientists also needed new ways to deliver vaccines. These included platforms like DNA, mRNA, and viral vectors, including adenovirus. The latter two are currently used in COVID-19 vaccines.

Although HIV vaccines have had mixed results overall, the most effective has been a prime-boost regimen. Researchers in 2012 found that it could reduce disease transmission by around 31% in phase three human trials. The concept underlying mixed vaccines is to present the bacteria or virus to the immune system differently. Because the immune system has a more comprehensive overview of the virus, it can tailor its response more effectively.

2. Mixing COVID-19 vaccines could help avoid immunity against the vaccine itself

Some types of vaccines use modified viruses to deliver the antigen. This means a person's immune system can attack the carrier virus because it's also a foreign virus. Mixing COVID-19 vaccine doses could help reduce this risk. Johnson & Johnson and AstraZeneca's vaccines are two examples of virus-based COVID-19 vaccines. They utilize an adenovirus — one of the culprits of the common cold. Scientists changed the virus to carry coronavirus spike proteins that trigger an immune response to COVID-19.

However, the immune system may instead respond to the adenovirus. Although this isn't dangerous, it may make the vaccine less effective. The immune system might detect the complete virus vector and jump into action to eliminate it from the body. Therefore, the vaccine has had zero or little opportunity to trigger an immune response against the coronavirus spike protein. Essentially, this makes the vaccine less efficient when used more than once. Scientists can circumnavigate the risk by using adenoviruses that humans haven't encountered. For example, AstraZeneca uses a chimpanzee adenovirus. Because of these effects, following initial vaccination, it's optimal to change the vaccine type, for example, to an mRNA or protein-based vaccine.

3. Mixing vaccines triggers a stronger and better response

Mixing doses may also provide stronger protection that outlasts that of traditional approaches. Vaccines help teach the immune system about the pathogen that causes the disease and enable it to mount an effective response. However, as explained, it can sometimes mistakenly respond to the harmless virus delivering the vaccine. But, mixing types of vaccines increases the immune response to coronavirus rather than the vector.

A pre-COVID-19 example of this was the Johnson & Johnson Ebola vaccine. The first dose uses an adenovirus, while the second uses a viral vector, in this case, a modified poxvirus. The scientists selected this approach because of the long-lasting protection it provided. Scientists have now investigated the effects of mixing and matching COVID-19 vaccine booster doses. They enrolled almost 500 individuals who had received an initial COVID-19 vaccination of Pfizer-BioNTech, Moderna, or the Johnson & Johnson vaccine. The participants received a booster shot of either the same or a different vaccine. The researchers found that all the participants produced an antibody response. However, those who received a booster of a different vaccine had similar or increased levels. Therefore, mixing vaccines has no detrimental effects on the immune system and, in many cases, prompts a stronger reaction.

4. Combining vaccines could help against COVID-19 variants

Since the pandemic began, multiple variants of COVID-19 have emerged. A mixed vaccine regimen could help foster an immune response that covers new variants and offers people comprehensive protection. Vaccines may protect against numerous coronavirus variants in the future, and mixing these could confer broad collective immunity. This approach would make it far more difficult for COVID-19 variants to spread or for new ones to emerge.

One such example is from Moderna. The pharmaceutical company has recently announced that their new version of their original COVID-19 vaccine seems to provide better and more long-lasting protection against variants. The new bivalent vaccine targets the original coronavirus strain and the beta variant. Initial study results suggest that it produces high levels of antibodies that can neutralize the viruses, and the protection extends for months. However, the results have not been independently peer-reviewed as yet. So, although these results are encouraging, the approach needs further research to confirm its benefits.

5. Mixing and matching means greater flexibility

One of the greatest challenges of the pandemic has been vaccine roll-out on a global scale. However, a mixed vaccine approach offers more flexibility and allows for speedier distribution.

Countries have had different success rates with their vaccination programs. For example, the U.K. and U.S. have managed to vaccinate large portions of their populations, whereas other countries have struggled. This is partly due to supply inequalities, issues with vaccine distribution, and problems with the cold chain — the process of keeping vaccines at a stable temperature throughout transport and storage.

A mixed vaccine approach would allow countries to use different types of vaccines, depending on what's available. It would also be easier to store and transport different vaccines, as they wouldn't all need to be kept at ultra-low temperatures.

For example, the Pfizer vaccine requires stringent storage at -70ºC (-94ºF), while the Moderna vaccine is lower maintenance and requires -20ºC (-4ºF). In contrast, the storage of the Johnson & Johnson vaccine is comparatively warm at around 2ºC or 36ºF.

A mixed vaccine approach could help supply vaccines to people in hard-to-reach areas with little infrastructure. It would also be beneficial in cases where electric power is scarce or unavailable.

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