Can new vaccines be better at fighting different variants of the coronavirus? 5 questions and answers

The first three coronavirus vaccines gained emergency use authorization in the United States more than a year ago. So far, no other vaccines have been put into use – but that will soon change. More than 40 vaccines are undergoing clinical trials in the United States, which employ several different approaches to protect people from Covid-19. Researchers Vaibhav Upadhyay and Krishna Mallela have been studying the spike protein of the coronavirus since the beginning of the pandemic and are developing therapies to stop the pandemic – and have answered questions about what the future holds.

1. Why are companies still working on new vaccines?

One of the main reasons new vaccines are important is the continuous emergence of new variants. Most of the differences between the variants are changes in the spike protein, which is on the surface of the virus and helps it to enter and infect cells. Some of these small changes in the spike protein allowed the coronavirus to infect human cells more efficiently – these changes also make previous vaccines or infections with Covid-19 provide less protection against the new variants. Newer, updated vaccines may be better at detecting these different spike proteins and more effective at protecting against new variants.

2. What types of vaccines are in progress?

So far, 38 vaccines have been approved worldwide – in the US, three have been approved. There are currently 195 vaccine candidates in different stages of development worldwide, of which 41 are in clinical trials in the US. Vaccines against SARS-CoV-2 can be divided into four classes: whole virus, viral vector, protein-based, and nucleic acid vaccine.

Whole virus vaccines generate immunity through a complete, albeit weakened, SARS-CoV-2 virus – called inactivated or attenuated. There are currently two such vaccines in clinical trials in the US. Viral vector vaccines are a variation on this approach – instead of using the entire coronavirus, they use a modified version of a harmless adenovirus that carries part of the coronavirus’ spike protein. Johnson & Johnson vaccine is a viral vector vaccine and there are 15 more candidates in this category in US clinical trials.

Protein-based vaccines use only the spike protein or part of the spike protein to generate immunity. As the spike protein is one of the most functionally important parts of the coronavirus, an immune response that targets just that part is enough to prevent or overcome an infection. The US currently has five protein-based vaccines in clinical trials.

Nucleic acid-based vaccines are currently the most used in the US. They are made of genetic material, such as DNA or RNA, which encodes the spike protein of the coronavirus. When a person receives it, their body reads the genetic material and produces the spike protein, which triggers an immune response. There are 17 RNA and two DNA vaccines in clinical trials in the US.

3. Will new vaccines be better than existing ones?

Moderna, Pfizer and J&J vaccines are based on the original variant of the coronavirus and are less potent against new strains. Vaccines based on new variants would provide better protection than existing vaccines and some are in development. Nucleic acid-based vaccines are the easiest to update and make up the majority of variant-targeted vaccines. Moderna has already produced a vaccine that contains mRNA from both the Beta and Omicron variants, and recently published clinical data proves that it is more effective against newer variants than Moderna’s original vaccine.

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

4. What are the benefits of whole virus vaccines?

Nucleic acid and protein-based vaccines use only the spike protein to produce an immune response. With a whole virus vaccine, the immune system not only recognizes the spike protein but also all other parts of the coronavirus, which allows it to quickly generate an immune response that involves several different branches of the immune system and that lasts longer.

Another benefit of whole virus vaccines and viral vectors is their ease of storage and shipping. Vaccines from viral vectors can be stored in a common refrigerated environment for months, sometimes years. In comparison, Moderna and Pfizer mRNA vaccines must be stored and shipped at ultra-low temperatures. These infrastructure requirements make whole virus vaccines much more viable for use in remote locations around the world.

5. What are the disadvantages of whole virus vaccines?

There are some disadvantages to whole virus vaccines. To produce vaccines from inactivated viruses, a huge amount of coronavirus must first be produced and then inactivated. There is a small but legitimate biohazard associated with the production of many live coronaviruses. A second disadvantage is that inactivated virus vaccines and viral vectors may not produce strong protection in immunocompromised patients.

Finally, the production of whole virus vaccines requires a lot more work compared to the production of mRNA vaccines – you need to grow, purify and inactivate the virus while carefully checking the quality of each step. This long production process makes it difficult to obtain 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 nucleic acid-based or protein-based vaccine code.

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