Nanobodies designed against influenza virus

The influenza virus, in its many variants, is a threat to global health and represents a constant challenge due to its high zoonotic potential. The H1N1 virus unleashed a pandemic in 2009 and continues to persist today with seasonal outbreaks. It is currently responsible for eighty percent of flu hospitalizations in countries such as Argentina, which underscores the need for tools complementary to vaccination to prevent and treat these diseases.

As a result of interdisciplinary work, the Viral Biotechnology group of the Bahía Blanca Biochemical Research Institute (INIBIBB), affiliated with the National Scientific and Technical Research Council (CONICET) and the National University of the South (UNS), in Argentina, managed to develop and characterize a series of ten molecules from llamas vaccinated against influenza. The team, led by CONICET researcher Mariana Puntel, believes that the isolated genes could perhaps be inoculated into humans to combat various viruses of the H1N1 subtype.

“This study offers a series of promising therapeutic candidates to combat H1N1 influenza virus infections and develop innovative technologies for the prevention and treatment of viral diseases,” Puntel emphasizes. The work was developed in close collaboration with the INCUINTA group linked to the Institute of Virology and Technological Innovations (IVIT), dependent on CONICET and the National Institute of Agricultural Technology (INTA), led by CONICET researcher Viviana Parreño.

In their work, the scientists were able to characterize monoclonal nanoantibodies that were effective in the prophylaxis of infection with the H1N1 influenza virus. In particular, they identified four therapeutic nanoantibodies derived by genetic engineering from heavy chain immunoglobulins present in llamas and other camelid species, each with different binding and neutralization capacities towards different regions of influenza viruses, allowing them to offer broad protection against this pathogen.

It is noteworthy that llama-derived nanoantibodies are ten times smaller than the best-known antibodies. They are monoclonal and have high stability and solubility, making them an attractive tool for the development of formulations that boost immunity in a complementary way to vaccination, or as diagnostic tools.

“The nanoantibodies we developed are candidates for use as active agents in prophylactic and therapeutic formulations. In particular, we are working on intranasal administration by drop, and we are studying their implementation in nebulizable formulations,” explains Puntel.

Mariana Puntel (right), director of the Viral Biotechnology group at INIBIBB, with doctoral student Luana Homann. (Photo: Pía Squarcia / CCT Bahía Blanca)

The results of the research represent a step forward in the development of new technologies capable of inhibiting viral replication of a wide range of influenza A virus strains. In addition, it is the first time that a nanoantibody has been described that provides sterilizing immunity against this virus at very low doses. One of the nanoantibodies identified was shown to confer in vivo protection at doses ten times lower than those described to date with this type of experimental treatment. This level of protection translates into a decrease to undetectable levels of the viral load in the lungs of treated mice on day four after exposure to the virus.

“After the tests carried out, no traces of virus were found in the mice treated intranasally and then infected. That is why we say that we were able to identify an ideal prophylactic candidate and we are excited that these results will be replicated in future trials,” concludes Puntel.

The study is titled “Anti-hemagglutinin monomeric nanobody provides prophylactic immunity against H1 subtype influenza A viruses.” It has been published in the academic journal PLoS ONE. (Source: CONICET. CC BY 2.5 AR)