The COVID-19 vaccination developed by Yeast might increase accessibility

The COVID-19 vaccination developed by Yeast might increase accessibility ...

Many people in wealthy countries have been vaccinated against Covid-19, but some areas in the world still need vaccination. A new vaccination developed at MIT and Beth Israel Deaconess Medical Center may help in these efforts, offering a simple, easy-to-store alternative to RNA vaccinations.

The researchers conclude that the vaccination, which includes fragments of the SARS-CoV-2 spike protein identified on a viral particle, enlicited a strong immune response and protected animals against a viral challenge.

The vaccine was designed to be developed by yeast using fermenting facilities that exist around the world. The Serum Institute of India, the world''s largest manufacturer of vaccinations, is now producing large quantities of the vaccine and intends to run a clinical trial in Africa.

There is still a very large population who does not have access to Covid vaccines. Protein-based subunit vaccinations are a low-cost, well-established technology that can provide a consistent supply, according to J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering at the University of Massachusetts, who is a member of the MGH, MIT, and Harvard.

Senior authors of the paper, which appears today in Science Advances, are: MIT graduate students Neil Dalvie and Sergio Rodriguez-Aponte, and Lisa Tostanoski, a postdoc at BIDMC.

Optimizing manufacturability

Loves lab working closely with Barouchs lab at BIDMC started developing a Covid-19 vaccine in early 2020. They intended to develop a vaccine that would be not only effective but also straightforward to develop. To this end, they focused on protein subunit vaccinations, a type of vaccination that consists of small pieces of viral proteins. Several existing vaccines, including one for Hepatitis B, have been implemented using this approach.

Subunit vaccinations might assist with some of the hesitancy surrounding vaccines based on newer technologies, according to Love.

Protein subunit vaccines have another advantage because they can often be stored under refrigeration and do not require the same ultracold storage temperatures as RNA vaccinations.

A small piece of the SARS-CoV-2 spike protein, the receptor-binding domain (RBD), was used before the epidemic, and studies in animals indicated that this protein fragment alone would not produce a strong immune response, thus the researchers decided to display many copies of the protein on a viral particle. The hepatitis B surface antibody was used as their scaffold, and showed that when coated with SARS-CoV-2 RBD fragments this particle produced a much stronger response than the RBD protein on its own

The researchers wanted to ensure that their vaccines were organized smoothly and efficiently. Many protein subunit vaccinations are made using mammalian cells, which can be more difficult to work with. The MIT team developed the RBD protein so that it could be produced by the yeastPichia pastoris, which is relatively easy to grow in an industrial bioreactor.

The RBD protein fragment and the hepatitis B particle can be assembled separately in yeast. The researchers added a special peptide tag to each component, which allows RBD fragments to be attached to virus particles after each incident.

Pichia pastorisis is the practice of bioreactors around the world, where they then sent their yeast cells to the Serum Institute, which quickly increased production.

One of the key issues that separates our vaccine from other vaccinations is that even the best facilities to produce vaccines in these yeast organisms exist in parts of the world where vaccines are still most effective today.

A modular process

In a small dose of nonhuman primates, the researchers combined the vaccine with adjuvants that are already used in other vaccines: either aluminum hydroxide (alum) or a combination of alum and another adjuvant called CpG.

The researchers found that when animals were exposed to SARS-CoV-2, viral loads were much lower than those observed in unvaccinated animals.

For the first phase of the trial, researchers used a RBD fragment, which was based on the sequence of the original SARS-CoV-2 strain that was discovered in late 2019. That vaccine has been used in a phase 1 clinical trial in Australia. Since then, the researchers have combined two mutations (similar to those identified in the natural Delta and Lambda variants) that the team previously described to improve production and immunogenicity compared to the ancestral sequence.

According to researchers, the method of attaching an immunogen RBD to a virus-like particle provides a plug-and-display mechanism that might be used to develop similar vaccinations.

Mutations that were previously seen in some of the new variants might be added to the RBD, but the whole framework will be unchanged, and new vaccine candidates might be made, according to Rodriguez-Aponte. That shows the versatility of the process and how efficient you can modify and make new candidates.

If clinical trials conclude that the vaccination provides a safe and effective alternative to existing RNA vaccinations, the researchers hope that it may not only be beneficial for vaccinating people in countries that have limited access to vaccines, but also enable the creation of boosters that would protect against a wider variety of SARS-CoV-2 strains and other coronaviruses.

According to Love, this modularity does not include modifying to new variations or introducing a more pan-coronavirus protective booster.

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