The first three coronavirus vaccines were granted 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 in clinical trials in the United States, which use several different approaches to protect people against Covid-19. Researchers Vaibhav Upadhyay and Krishna Mallela have been studying the coronavirus spike protein since the start of the pandemic and developing therapies to stop the pandemic – and answered questions about what the future holds.
1. Why are companies still working on new vaccines?
The continued emergence of new variants is one of the main reasons why new vaccines are important. Most of the differences between the variants are changes in the spike protein, which sits on the surface of the virus and helps it 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 cause previous Covid-19 vaccines or infections to offer less protection against newer variants. Newer, updated vaccines may be better at detecting these different spike proteins and better at protecting against newer variants.
2. What types of vaccines are in progress?
So far, 38 vaccines have been approved worldwide – in the United States, three have been approved. There are currently 195 candidate vaccines in various stages of development worldwide, 41 of which are in clinical trials in the United States. SARS-CoV-2 vaccines 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 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 part of the coronavirus spike protein. The Johnson & Johnson vaccine is a viral vector vaccine and there are 15 other candidates in this category in clinical trials in the United States.
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 only this part is sufficient to prevent or defeat an infection. The United States currently has five protein-based vaccines in clinical trials.
Nucleic acid vaccines are currently the most widely used in the United States. They are made up of genetic material, such as DNA or RNA, which codes for the coronavirus spike protein. 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 United States.
3. Will new vaccines be better than existing vaccines?
The Moderna, Pfizer and J&J vaccines are based on the original variant of the coronavirus and are less potent against newer strains. Vaccines based on new variants would offer better protection than existing vaccines and some are under development. Nucleic acid-based vaccines are the easiest to update and constitute the majority of variant-targeted vaccines. Moderna has already produced a vaccine containing mRNA of the Beta and Omicron variants, and recently published clinical data proves that it is more effective against the new variants than Moderna’s original vaccine.
Although updating nucleic acid vaccines is important, some research suggests that viral vector or whole virus vaccines may be more effective against newer variants, without requiring 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, allowing it to quickly generate an immune response that involves several different branches of the immune system and lasts longer.
Another advantage 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. By 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?
Whole virus vaccines have some disadvantages. To produce vaccines from inactivated viruses, a huge amount of coronavirus must first be produced and then inactivated. There is a small but legitimate biological risk associated with the production of many live coronaviruses. A second drawback is that inactivated viral vaccines and viral vectors may not produce strong protection in immunocompromised patients.
Finally, producing whole virus vaccines is much more labor intensive than producing mRNA vaccines – you have 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 vaccine. For the same reasons, redesigning or updating whole-virus vaccines for future variants is more difficult than simply changing the code of the nucleic acid-based or protein-based vaccine.