WRAIR Researchers Identify Nano-sized Antibodies in Sharks Able to Broadly and Potently Neutralize a Range of Sarbecoviruses

Scientists with the Walter Reed Army Institute of Research (WRAIR) have found that immunizing nurse sharks with experimental SARS-CoV-2 vaccines elicited a set of unique nano-sized antibodies that broadly neutralize a range of viruses in the SARS-CoV family and confer passive immune protection in a mouse virus challenge model. Findings were published in Nature Communications.

SARS-CoV-2 continues to evolve and evade, presenting a need for next-generation diverse countermeasures. WRAIR’s Emerging Infectious Diseases Branch (EIDB) is leading efforts to develop monoclonal antibody products that detect, prevent and treat COVID-19. Some animal families, including llamas, camels, and sharks, produce antibodies with binding domains that are less than a quarter of the size of binding domains from conventional antibodies such as those found in humans. These ‘nanobodies’ can work inside cells and can be delivered to tissues in the body that larger antibodies can’t. Their exceptionally small size and high stability also make it easier for researchers to develop into countermeasure products.

The recent study is a collaboration with a team at the University of Maryland School of Medicine. Groups of nurse sharks were immunized with one of three experimental SARS-CoV-2 vaccines developed by WRAIR: a recombinant receptor binding domain (RBD) vaccine, an RBD-ferritin (RFN) vaccine, or a spike protein ferritin nanoparticle (SpFN) vaccine. All three vaccine immunogens were based on the original SARS-CoV-2 sequence. Researchers produced two molecules, ShAb01 and ShAb02, from these vaccinated sharks that were shown in vitro to potently cross-neutralize the original SARS-CoV-2 virus, as well as Alpha, Beta, Delta, Omicron BA.1 and BA.5 variants of concern, in addition to SARS-CoV-1.

To assess the ability of the ShAb molecules to protect against COVID19 infections, scientists carried out an in vivo protection study, injecting mice with ShAb01 or ShAb02 then challenging them with viral infection. Both ShAbs provided protection in the mice as demonstrated by substantially lower viral load in their lungs than the control group.

Researchers then analyzed the structure of the nanobodies to identify the specific binding properties of each group. Using this structural information, they designed a set of multi-specific antibodies combining the desirable features of ShAb01 and ShAb02. These new molecules could provide greater capacity to resist SARS-CoV-2 viral variation and possibilities for development for future diagnostic, therapeutic, or preventive use.

Disclaimer: Research was conducted under an IACUC-approved animal use protocol in an AAALAC International - accredited facility with a Public Health Services Animal Welfare Assurance and in compliance with the Animal Welfare Act and other federal statutes and regulations relating to laboratory animals.