A new protein subunit vaccine established at MIT and Beth Israel Deaconess Medical Center may use an economical, easy-to-store, and efficient option to RNA vaccines for Covid-19. To that end, they focused on protein subunit vaccines, a type of vaccine that consists of little pieces of viral proteins. For their subunit vaccine, the researchers chose to utilize a small piece of the SARS-CoV-2 spike protein, the receptor-binding domain (RBD). Lots of protein subunit vaccines are produced using mammalian cells, which can be more difficult to work with. For that vaccine, the scientists used an RBD piece that was based on the series of the initial SARS-CoV-2 strain that emerged in late 2019.
A brand-new protein subunit vaccine developed at MIT and Beth Israel Deaconess Medical Center may provide an inexpensive, easy-to-store, and effective option to RNA vaccines for Covid-19. Visualized is a schematic of the vaccine. Credit: Jose-Luis Olivares, MIT, and figures courtesy of the researchers
The protein subunit vaccine, which can be manufactured using engineered yeast, has revealed promise in preclinical studies.
While many individuals in wealthier countries have actually been immunized against Covid-19, there is still a need for vaccination in much of the world. A new vaccine developed at MIT and Beth Israel Deaconess Medical Center might help in those efforts, offering a low-cost, easy-to-store, and effective option to RNA vaccines.
In a brand-new paper, the scientists report that the vaccine, which comprises fragments of the SARS-CoV-2 spike protein arrayed on a virus-like particle, elicited a strong immune response and secured animals versus viral obstacle.
The vaccine was created so that it can be produced by yeast, utilizing fermentation centers that currently exist around the world. The Serum Institute of India, the worlds largest maker of vaccines, is now producing large quantities of the vaccine and prepares to run a scientific trial in Africa.
” Theres still a huge population that does not have access to Covid vaccines. Protein-based subunit vaccines are a low-cost, well-established innovation that can supply a constant supply and is accepted in many parts of the world,” says J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering at MIT and a member of the Koch Institute for Integrative Cancer Research and the Ragon Institute of MGH, MIT, and Harvard.
Love and Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center (BIDMC) and a professor at Harvard Medical School, are the senior authors of the paper, which was published on March 16, 2022, in Science Advances. The papers lead authors are MIT college students Neil Dalvie and Sergio Rodriguez-Aponte, and Lisa Tostanoski, a postdoc at BIDMC.
Optimizing manufacturability
Loves laboratory, working closely with Barouchs laboratory at BIDMC, started dealing with a Covid-19 vaccine in early 2020. Their objective was to produce a vaccine that would be not just effective however likewise simple to produce. To that end, they focused on protein subunit vaccines, a type of vaccine that consists of small pieces of viral proteins. Numerous existing vaccines, consisting of one for hepatitis B, have been made using this method.
” In places in the world where cost stays a challenge, subunit vaccines can address that. They could also deal with a few of the hesitancy around vaccines based on newer innovations,” Love says.
Another advantage of protein subunit vaccines is that they can typically be stored under refrigeration and do not need the ultracold storage temperatures that RNA vaccines do.
For their subunit vaccine, the scientists decided to use a little piece of the SARS-CoV-2 spike protein, the receptor-binding domain (RBD). Early in the pandemic, research studies in animals recommended that this protein fragment alone would not produce a strong immune response, so to make it more immunogenic, the group chose to show lots of copies of the protein on a virus-like particle. They chose the hepatitis B surface area antigen as their scaffold, and revealed that when covered with SARS-CoV-2 RBD fragments this particle produced a much stronger reaction than the RBD protein by itself.
The researchers also wished to ensure that their vaccine could be produced quickly and efficiently. Numerous protein subunit vaccines are produced using mammalian cells, which can be harder to work with. The MIT team designed the RBD protein so that it could be produced by the yeast Pichia pastoris, which is relatively easy to grow in a commercial bioreactor.
Each of the 2 vaccine parts– the RBD protein fragment and the liver disease B particle– can be produced independently in yeast. To each part, the scientists included a specialized peptide tag that binds with a tag discovered on the other component, enabling RBD pieces to be connected to the virus particles after each is produced.
Pichia pastoris is currently utilized to produce vaccines in bioreactors worldwide. Once the scientists had their engineered yeast cells prepared, they sent them to the Serum Institute, which ramped up production quickly.
” One of the essential things that separates our vaccine from other vaccines is that the facilities to make vaccines in these yeast organisms currently exist in parts of the world where the vaccines are still most needed today,” Dalvie states.
A modular procedure
As soon as the researchers had their vaccine candidate prepared, they tested it in a little trial in nonhuman primates. For those research studies, they integrated the vaccine with adjuvants that are already used in other vaccines: either aluminum hydroxide (alum) or a mix of alum and another adjuvant called CpG.
In those research studies, the scientists showed that the vaccine generated antibody levels comparable to those produced by a few of the approved Covid-19 vaccines, consisting of the Johnson and Johnson vaccine. They also discovered that when the animals were exposed to SARS-CoV-2, viral loads in immunized animals were much lower than those seen in unvaccinated animals.
For that vaccine, the scientists utilized an RBD piece that was based on the series of the original SARS-CoV-2 strain that emerged in late 2019. That vaccine has been checked in a phase 1 scientific trial in Australia. Ever since, the researchers have actually incorporated 2 anomalies (comparable to ones determined in the natural Delta and Lambda variants) that the group formerly discovered to enhance production and immunogenicity compared to the ancestral sequence, for the organized phase 1/2 medical trials.
The method of attaching an immunogen RBD to a virus-like particle uses a “plug and screen”- like system that might be used to create similar vaccines, the researchers state.
” We might make mutations that were seen in some of the new versions, include them to the RBD but keep the entire structure the exact same, and make new vaccine candidates,” Rodriguez-Aponte states. “That shows the modularity of the process and how efficiently you can edit and make brand-new prospects.”
If the medical trials show that the vaccine offers a reliable and safe option to existing RNA vaccines, the researchers hope that it might not only show beneficial for immunizing people in nations that presently have restricted access to vaccines, but also make it possible for the creation of boosters that would offer protection against a wider range of SARS-CoV-2 pressures or other coronaviruses.
” In principle, this modularity does permit factor to consider of adapting to new variants or providing a more pan-coronavirus protective booster,” Love says.
Referral: “SARS-CoV-2 receptor binding domain showed on HBsAg virus– like particles elicits protective resistance in macaques” by Neil C. Dalvie, Lisa H. Tostanoski, Sergio A. Rodriguez-Aponte, Kawaljit Kaur, Sakshi Bajoria, Ozan S. Kumru, Amanda J. Martinot, Abishek Chandrashekar, Katherine McMahan, Noe B. Mercado, Jingyou Yu, Aiquan Chang, Victoria M. Giffin, Felix Nampanya, Shivani Patel, Lesley Bowman, Christopher A. Naranjo, Dongsoo Yun, Zach Flinchbaugh, Laurent Pessaint, Renita Brown, Jason Velasco, Elyse Teow, Anthony Cook, Hanne Andersen, Mark G. Lewis, Danielle L. Camp, Judith Maxwell Silverman, Gaurav S. Nagar, Harish D. Rao, Rakesh R. Lothe, Rahul Chandrasekharan, Meghraj P. Rajurkar, Umesh S. Shaligram, Harry Kleanthous, Sangeeta B. Joshi, David B. Volkin, Sumi Biswas, J. Christopher Love and Dan H. Barouch, 16 March 2022, Science Advances.DOI: 10.1126/ sciadv.abl6015.
Researchers from the Serum Institute and SpyBiotech likewise contributed to the paper. The research study was moneyed by the Bill and Melinda Gates Foundation and the Koch Institute Support (core) Grant from the National Cancer Institute.
