March 21stst 2022
Jeremy D. Bailoo
While some countries appear to be emerging from the pandemic, many developing countries continue to struggle to vaccinate their citizens as they have limited access to the vaccine. Now, thanks to animal research, an inexpensive, easy-to-store, and effective alternative to RNA vaccines — a protein subunit vaccine — may be on the horizon.
The researchers report that the protein subunit vaccine, which includes fragments of the SARS-CoV-2 spike protein placed on a virus-like particle, elicited a strong immune response and protected the animals against viral challenge.
“In places around the world where cost remains a challenge, subunit vaccines can solve this problem. They could also answer some of the hesitation around vaccines based on new technologies,” says Love, author of the article. Other popular subunit vaccines include those for hepatitis B and acellular pertussis.
Another advantage of protein subunit vaccines is that they can often be stored under refrigeration and do not require the ultra-cold storage temperatures of RNA vaccines.
For the subunit vaccine, the researchers decided to use a small piece of SARS-CoV-2’s spike protein, the receptor binding domain (RBD). At the start of the pandemic, studies with the animals suggested that this protein fragment alone would not produce a strong immune response, and so the team decided to display many copies of the protein on a virus-like particle (a scaffold). They placed the SARS-CoV-2 RBD fragment on a scaffold created by the body when exposed to hepatitis B (an antigen) and showed that when coated with a SARS-CoV-2 fragment RBD, this particle generated a much stronger response than the protein RBD alone.
Once the researchers had prepared their vaccine candidate, they tested it in a small trial in non-human primates. For these studies, they combined the vaccine with a substance that enhances the body’s immune response (adjuvant) and is commonly used in other vaccines: either aluminum hydroxide or a combination of alum and another adjuvant called CpG.
In these studies, the researchers showed that the vaccine generated levels of antibodies similar to those produced by some of the approved Covid-19 vaccines, including the Johnson and Johnson vaccine. They also found that when animals were exposed to SARS-CoV-2, viral loads in vaccinated animals were much lower than those seen in unvaccinated animals.
For the vaccine mentioned above, researchers used an RBD fragment based on the sequence of the original SARS-CoV-2 strain that emerged in late 2019. This vaccine was tested in a phase 1 clinical trial in Australia. A phase 1 clinical trial is a test performed on fewer than 100 adult human volunteers. Since then, researchers have incorporated two mutations (similar to those identified in the natural variants Delta and Lambda) that the team had previously found to improve production and immunogenicity over the ancestral sequence, for phase clinical trials. 1 and phase 2 planned. A phase 2 clinical trial is similar to phase 1 trials, but with a few hundred adult human volunteers.
The vaccine was designed to be able to be produced by yeast, using fermentation facilities that already exist around the world. The Serum Institute of India, the world’s largest vaccine manufacturer, is currently producing large quantities of vaccines and plans to conduct a clinical trial in Africa.
If clinical trials show the vaccine offers a safe and effective alternative to existing RNA vaccines, researchers hope it may not only prove useful for vaccinating people in countries that currently have limited access to vaccines. They also hope it would lay the groundwork for creating boosters that offer protection against a wider variety of strains of SARS-CoV-2 or other coronaviruses. This is important because what we have learned over the past 3 years is that being prepared saves lives!
**Content taken from press release and edited for style