Yeast-Expressed, RBD-Based Vaccine Provides Robust Immune Responses Against SARS-CoV-2

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The ongoing coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 190 million cases worldwide. Of these, over 4 million people died from the infection.

SARS-CoV-2 vaccine development is focused on identifying stable, accessible, and inexpensive candidates for global use, particularly in low and middle income countries.

Now a new study has been published in the journal Science immunology reports on the efficacy of a rapidly scalable, novel vaccine based on SARS-CoV-2 specific receptor binding domain (RBD) formulated with 3M-052 alum adjuvant. The formulation induced a robust immune response and protection against SARS-CoV-2 in rhesus monkeys.

Researchers at Yerkes National Primate Research Center at Emory University, Infectious Disease Research Institute (IDRI), 3M, and Texas Children’s Hospital’s Center for Vaccine Development at Baylor College of Medicine were the first to demonstrate the combination of yeast expression technology and a new adjuvant formulation to produce a COVID-19 vaccine candidate. Affordable and easy to manufacture on a large scale, the new vaccine could be a big breakthrough.

The formulation of the recombinant protein SARS-CoV-2 RBD

Beta coronavirus (CoV) infection in humans causes symptoms that range from mild strains caused by the common cold to severe acute respiratory syndromes (SARS) caused by highly virulent strains. People at risk, such as the elderly and those with comorbidities, can have severe symptoms and are at higher risk of death.

The SARS-CoV-2 enters the cells via the human angiotensin converting enzyme 2 (ACE2) receptor, using the receptor binding domain (RBD) of its spike protein. Therefore, the S protein is the primary target for vaccine development.

Immunogens that are stabilized in their pre-fusion state produce potent virus neutralizing activity after vaccination. The RBD in the spike protein is the most dominant target for neutralizing SARS-CoV-2. There is also a yeast called Pichia pastoris, expressed RBD-based vaccine against coronavirus of severe acute respiratory syndrome (SARS-CoV) in mice.

Pichia pastoris.  Image source: Rattiya Thongdumhyu / Shutterstock

Pichia pastoris. Image source: Rattiya Thongdumhyu / Shutterstock

Yeast expression is widespread for hepatitis B vaccines in low and middle income countries and this shows the advantage for the rapid development and manufacture of yeast based SARS-CoV-2 vaccines.

The vaccine

The researchers combined Baylor’s SARS-CoV-2 RBD vaccine with recombinant protein formulation with IDRI’s aluminum-based formulation of 3M’s toll-like receptor 7 and 8 agonists 3M-052 (3M-052 / Alum) to boost the immune response against SARS-CoV. 2, which increases the effectiveness of the vaccine against COVID-19.

When testing the vaccine on rhesus monkeys, the team found that the 3M-052 / alum formulation elicited a significant and robust overall immune response than alum alone. It led to a significant reduction in SARS-CoV-2 virus particles in the upper and lower airways. It also reduced the severity of lung disease compared to unvaccinated animals.

In addition, the new and promising vaccine blocked an increase in intermediate blood monocytes CD14 + CD16 ++ after SARS-CoV-2 as well as Fractalkin, MCP-1 and TRAIL in the plasma. In addition, the RBD-specific plasma cells accumulated in the draining lymph nodes and not, as previously determined, in the bone marrow.

“Together, these data show that a yeast-expressed RBD-based vaccine + 3M-052 alum offers robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate,” the researchers noted in the Study notes.

The team believes that the vaccine, which contains a recombinant RBD protein with its novel 3M-052 adjuvant formulation, may be effective against SARS-CoV-2, including its emerging variants. This is because the vaccine can induce and stimulate both neutralizing antibodies and CD8 + T cells, which can kill the virus when it enters the cells.

“Our study supports the testing of an RBD-based immunogen with adjuvant with 3M-052 alum, which could offer itself as an inexpensive, scalable and thermostable SARS-CoV-2 vaccine,” the team concluded in the study.



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