2021-05-30| PartnerCOVID-19R&D

Is Heterologous Prime-Boost of COVID-19 Vaccines the Way to Go?

by GeneOnline
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With new COVID waves and global vaccine shortages, Spain and the UK are leading studies that are investigating the effect of mixing COVID vaccine brands. Preliminary results of both these trials are promising and shows the benefits of mixing vaccine regimens of different brands. These studies certainly spark confidence in prime-boost immunizations with heterologously mixed vaccines.

The US Centers for Disease Control and Prevention (CDC) has warned against the mixing of vaccines, with the exception of those that are previously administered and are experiencing shortages. However, currently, the huge global demand has severely curtailed COVID vaccine supplies. It’s about time to mitigate these exceptional situations that weaken the speed of worldwide vaccination.

In light of these events, the global interest in heterologous prime-boost COVID-19 vaccination arises. Together with the shifting recommendations on the use of AstraZeneca vaccine (Vaxzevria, using a harmless chimpanzee adenovirus), several EU countries are advising those previously primed with Vaxzevria should now receive an alternative vaccine, for example, Pfizer vaccine (Comirnaty, using mRNA technology) as their second dose, administered according to a heterologous prime-boost schedule. Two world-leading studies recently unveiled the safety and efficacy rates when these brands were mixed.


Deployment of Heterologous Prime-Boost Trials Worldwide

Recently, two trials have helped to understand the reactogenicity and safety when different combinations of approved COVID vaccines are administered as consecutive doses. The first trial is the Com-COV (EudraCT 2020-005085-33) study, funded by the UK Vaccine Task Force and the National Institute for Health Research. It aims to figure out the response of the immune system comprising of T cell profiles when people are primed with one type of vaccine and then boosted with another.

Common vaccine reactions like fever were also examined after such a mixed schedule. The study recruited up to 830 participants in the initial phase and subsequently recruited an additional 1,050 participants, all aged over 50. Using animal experiments, the program has already confirmed that the vaccine combinations of AstraZeneca and Pfizer can provide stronger immunity than two vaccine doses of the same brand. This study includes AstraZeneca, GlaxoSmithKline, Pfizer, Novavax, Janssen, Medimmune, and MCM vaccines.

Another trial is CombiVacS (EudraCT 2021-001978-37) study sponsored by the Spanish clinical research network and Instituto de Salud Carlos III. The study opted to use AstraZeneca and Pfizer vaccines to explore the possibility of heterologous vaccination strategy and evaluated the safety and immunogenicity of a second dose of Pfizer vaccine in subjects that received the first dose of AstraZeneca vaccine.

About five hospitals in Madrid, Bilbao, and Barcelona took part in this trial, and a total of 676 volunteers aged 18 to 60 received the first dose of the AstraZeneca vaccine. Around two-thirds were randomly assigned to get the Pfizer vaccine for their second dose, and one-third served as a control group. The latter did not receive a booster shot, allowing for the two groups to be compared. The immune responses, as well as protection against COVID variants, were evaluated at 14 and 28 days after receiving the Pfizer vaccine.


Drive Comprehensive and Strong T-cell-focused Immunity

In early May, preliminary results of the trials involving more than 2000 participants were announced. The participants had shown higher levels of COVID spike protein-specific antibodies. These antibodies were further confirmed to be extraordinarily capable against COVID viruses, highlighting that the heterologous Prime-Boost modality using Pfizer vaccine as booster seems to elicit an immune response even stronger than the one most people generate after receiving two homologous doses or a single dose of AstraZeneca vaccine. The benefits of mixing two brands into one heterologous vaccination regimen are apparent and point towards a possibility of implementing a similar regimen in India, which is badly hit by the worst spreading COVID wave in recent times.


Transient Side Effects

Repeated doses of the AstraZeneca vaccine become increasingly less effective, owing to the immune response against its vector. It may also trigger stronger side effects. Looking at the cases of blood clots, nearly 20 countries consequently suspended the use of the AstraZeneca vaccine. Most people who received the first dose became unwilling to get the second.

For these reasons, ensuring the safety and efficacy of the first AstraZeneca dose and minimizing side effects have become one of the most difficult global issues to combat. Heterologous vaccine schedules may be the way to go. Even though the reactogenicity following the booster dose is greater with heterologous vaccinations as compared to their homologous counterparts, it’s reassuring to know that they are only short-term. Only below 2% of participants were found to show moderate side effects, and no hospitalizations resulted from those symptoms.

Furthermore, heterologous vaccinations could elicit immune responses more toward Th1-mediated immunity rather than Th2 mode, indicating that adverse events caused by Th2-type lung immunopathology can be reduced. Altogether, people who received the first AstraZeneca dose can be administered a Pfizer booster shot more safely and effectively.

Presently, over 1.6 billion vaccine doses had been delivered worldwide, with only twenty doses for every one hundred persons. Unfortunately, our world is far from being fully vaccinated, with some countries yet to report even single dosing. The gap across many countries is obvious. There are several barriers that real-world vaccination programs face now, besides the bottlenecks in the supply chain.

Heterologous vaccinations provide hope for long-term immunity against COVID by removing some of those obstacles away. Multiple vaccine options offer a more easy and fast way to maintain the defense against COVID and prolong protection, particularly if a third dose is required against COVID variants.

Lastly, from an economic perspective, this strategy facilitates simpler and cost-effective immunization efforts for countries that encounter safety and efficacy issues or instability in vaccine supplies. To win the battle against the virus, perhaps this mix and match strategy of COVID vaccination could lead us to victory.

Related Article: Sanofi, GSK Report Positive Trial Data for COVID-19 Vaccine

By Wei-Hao Su & Peter P.T. Chang

Review & Edits by GeneOnline


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