Yerkes Researchers Develop Low-Cost, Low-Dose RBD Trimer Protein-Based COVID-19 Vaccine Candidate

July 1, 2021

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Lisa Newbern

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Researchers at Yerkes National Primate Research Center, Emory University have developed a second COVID-19 vaccine candidate that induces a strong antibody response and provides protection in mice and monkeys. This vaccine, which is based on a protein platform, designed to be cost-effective and given in low dose, relies on a trimer model and an immune-stimulating substance, an adjuvant, to induce a long-lasting antibody response. The new vaccine likely won't require an annual booster, but can be used as one to increase effectiveness of currently available COVID-19 vaccines.

Results from this National Institute of Allergy and Infectious Diseases (NIAID)-funded study are published online in Nature Communications.

Lead researcher Rama Amara, PhD, and his team developed the two-dose vaccine by using a small region of the SARS-CoV-2 spike protein, the Receptor Binding Domain (RBD), where three copies of the protein (the trimer) are merged. The team then combined the trimer with the Infectious Disease Research Institute's (IDRI) aluminum-based adjuvant formulation of 3M's 3M-052 (3M-052/Alum), which has been shown to induce potent and long-lasting antibody response superior to alum alone in monkeys.

Initial studies in mice showed the trimeric form induced potent neutralizing antibodies and completely blocked SARS-CoV-2 infection with as little as one microgram of the protein. Following these encouraging study results in mice, the Amara team tested the RBD trimer COVID-19 vaccine in rhesus monkeys at Yerkes. The researchers gave four monkeys two doses of the RBD trimer plus 3M-052/alum and five monkeys two doses of the RBD trimer plus alum alone. The researchers gave the doses a month apart and then challenged the nine vaccinated animals and seven unvaccinated monkeys with SARS-CoV-2.

The virus replicated and caused lung inflammation in the unvaccinated animals, but the RBD trimer COVID-19 vaccine plus 3M-052/alum combination proved most effective in providing protection against SARS-CoV-2 replication and inflammation in the lungs, which is important to prevent the development of COVID-19. The antibodies the vaccine induces also showed strong neutralizing activity to block the infection against the Beta SARS-CoV-2 variant in a culture dish. Based on these results, the research team expects the effectiveness to extend to emerging coronavirus variants.

"Delivering the protein in trimeric form induces a much stronger neutralizing antibody response compared to single copy form and remains equally effective even when given at very low doses," says Amara. "Generating durable immune responses and neutralizing antibodies at low doses facilitates low cost, something important for worldwide vaccine distribution. Also important is having an option to boost vaccine effectiveness, such as the need that has been discussed for the mRNA (Moderna and Pfizer-BioNTech) and viral vector vaccines (J&J/Janssen). Our vaccine can fill that need," he continues. Amara is a researcher in Yerkes' Division of Microbiology and Immunology and the Emory Vaccine Center (EVC) as well as a Charles Howard Candler professor of microbiology and immunology at Emory School of Medicine (SOM).

Amara's Yerkes research team includes Nanda Kishore Routhu, PhD (postdoc), Narayanaiah Cheedarla, PhD (postdoc), Venkata Satish Bollimpelli, PhD (postdoc), and Sailaja Gangadhara, PhD (research associate), all four co-lead authors, as well as Ayalensh Shiferaw (research specialist). The recent Amara team vaccine studies have been done in close collaboration with Mehul Suthar, PhD, and his research team. Suthar is an assistant professor in the Emory School of Medicine Department of Pediatrics and an EVC researcher. In addition, the collaborative research team also includes Christopher Fox, PhD, IDRI, and Mark Tomai, PhD, 3M.

In addition to the NIAID grant, the RBD Trimer protein vaccine study reported in this release is supported in part by the Yerkes National Primate Research Center base grant from the NIH Office of the Director, Office of Research Infrastructure Programs as well as by the Fast Grants program.

Grant amounts (direct + indirect):

  • 3R01AI148378-01S1 $582,625/2 years
  • P51OD011132 $10,540,602/5 years
  • Fast grant 1, $250,000
  • Fast grant 2, $350,000

Note: The amounts listed above are for the full grants. Only a portion of the P51 will support infrastructure needs of the COVID-19 vaccine study reported in this news release.

Dedicated to discovering causes, preventions, treatments and cures, the Yerkes National Primate Research Center (NPRC), part of Emory University's Robert W. Woodruff Health Sciences Center, is fighting diseases and improving human health and lives worldwide. The center, one of only seven NPRCs the National Institutes of Health (NIH) funds, is supported by more than $74 million in research funding (all sources, fiscal year 2018). Yerkes researchers are making landmark discoveries in microbiology and immunology; neurologic diseases; neuropharmacology; behavioral, cognitive, and developmental neuroscience; and psychiatric disorders. Since 1984, the center has been fully accredited by the AAALAC International, regarded as the gold seal of approval for laboratory animal care. For more information about Yerkes and the seven NPRCs, visit and follow us at @NPRCnews.

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

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