Wednesday, May 4, 2022

Will new vaccines fight COVID variants better? 5 questions answered

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The first three coronavirus vaccines received emergency authorization more than a year ago. So far, no other vaccines have been used in the US – but that will soon change. More than 40 vaccines are being clinically tested in the US, using a number of different approaches to protect people from the coronavirus. Vaibhav Upadhyay and Krishna Mallela have been studying the coronavirus spike protein and developing COVID-19 therapeutics since the outbreak of the pandemic. Together they explain what vaccines are in development and why some of the vaccines should be better than those currently available.

A key reason why new vaccines matter — and why the world is still grappling with COVID-19 — is the constant emergence of new variants. Most of the differences between the variants are changes in the spike protein, which is found on the surface of the virus and helps it enter and infect cells.

Some of these small changes in the spike protein have allowed the coronavirus to infect human cells more efficiently. These changes have also meant that previous vaccinations or infections with COVID-19 offer less protection against the new variants. Updated or new vaccines could better recognize these different spike proteins and better protect against new variants.

To date, 38 vaccines have been approved worldwide, and the US has approved three of them. There are currently 195 vaccine candidates at various stages of development worldwide, of which 41 are in clinical trials in the US -based vaccines.

Whole virus vaccines generate immunity using a whole, albeit weakened – as inactivated or attenuated – SARS-CoV-2 virus. Two of these vaccines are currently in clinical trials in the United States. Viral vector vaccines are a variation on this approach. Instead of using the whole coronavirus, they use a modified version of a harmless adenovirus that carries pieces of the coronavirus spike protein. Johnson & Johnson’s vaccine is a viral vector vaccine and there are 15 other candidates in this category in clinical trials in the US.

Protein-based vaccines use only the spike protein or part of the spike protein to generate immunity. Since the spike protein is one of the functionally most important parts of the coronavirus, an immune response that targets only this one part is sufficient to prevent or overcome infection. Five protein-based vaccines are currently in clinical trials in the United States.

Nucleic acid-based vaccines are currently the most commonly used in the United States. These consist of genetic material such as DNA or RNA that codes for the spike protein of the coronavirus. Once a person receives one of these shots, their body reads the genetic material and produces the spike protein. This in turn creates an immune response. There are 17 RNA and two DNA vaccines in clinical trials in the United States. Some of these use the genetic material of newer variants, including updated versions of the Moderna and Pfizer vaccines.

Moderna, Pfizer and J&J vaccines are based on the original strain of the coronavirus and are less effective when faced with new variants. Vaccines based on new variants would offer better protection against these newer strains than existing vaccines, and some are under development. Nucleic acid-based vaccines are the easiest to update and make up the majority of variant-specific vaccines. Moderna has already produced a vaccine containing mRNA from both the beta and omicron variants, and some recently released clinical data shows that it is more effective than Moderna’s original vaccine against newer variants.

While updating of nucleic acid vaccines is important, some research suggests that viral vector or whole virus vaccines could be more effective against new variants – without the need for an update.

Nucleic acid and protein-based vaccines use only the spike protein to elicit an immune response. With a whole virus vaccination, the immune system not only recognizes the spike protein, but also all other parts of the coronavirus. The other parts of the virus help generate a powerful, long-lasting immune response that involves many different branches of the immune system.

Another advantage of whole virus and viral vector vaccines is the ease of storage and shipping. Viral vector vaccines can be stored for months, sometimes years, in ordinary household refrigerators. In comparison, Moderna and Pfizer’s mRNA vaccines must be stored and shipped at extremely low temperatures. These infrastructure requirements make whole-virus vaccines much more viable for use in remote locations in the United States as well as around the world.

There are some downsides to whole virus vaccines.

To make inactivated virus vaccines, you must first make a large batch of live coronaviruses and then inactivate them. There is a small but legitimate biohazard risk associated with the production of many live coronaviruses. A second disadvantage is that vaccines containing inactivated viruses and viral vectors may not provide strong protection in immunocompromised patients.

Finally, producing whole virus vaccines is much more labor intensive than producing mRNA vaccines. You must grow the virus, then clean it, and then inactivate it while carefully checking the quality at each step. This long production process makes it difficult to produce large quantities of the vaccine. For the same reasons, redesigning or updating whole-virus vaccines for future variants is more difficult than simply changing the code of nucleic acid- or protein-based vaccines.

Given the advantages and disadvantages of each vaccine type, we believe that virus-based vaccines could play an important role in creating long-lasting, broad-based immunity against a rapidly mutating virus. But easy-to-upgrade mRNA or protein-based approaches that can be tuned to the latest variants may also be a key to containing the spread of the pandemic. With vaccines of all kinds in the works, public health officials and governments around the world will have more tools at their disposal to deal with what the coronavirus brings next.

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By Vaibhav Upadhyay, Postdoctoral Researcher in Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus and Krishna Mallela, Professor of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus

This article was republished by The Conversation under a Creative Commons license. Read the original article.

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