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Progress in Adenovirus Monoclonal Neutralizing Antibody Research

ZhuHanBin Sun, Apr 21 2024 11:01 AM EST

Chinese researchers have made new advancements in the study of HAdV-55 monoclonal neutralizing antibodies. The findings were published in the international journal Emerging Microbes & Infections.

Human adenovirus (HAdV) is a common respiratory pathogen, with over 100 identified genotypes. In recent years, HAdV-55 has frequently caused outbreaks in military camps, hospitals, schools, and other densely populated areas. In 2012, an outbreak of HAdV-55 occurred in a certain location, leading to rumors of "SARS recurrence." HAdV-55 infection can cause acute respiratory diseases and even severe pneumonia, with no specific drugs currently available.

Monoclonal neutralizing antibodies are important for the prevention and treatment of acute viral diseases, with monoclonal neutralizing antibodies for diseases such as COVID-19 and respiratory syncytial virus already approved for use. However, research on HAdV-55 monoclonal neutralizing antibodies has been limited, mainly due to the scarcity of convalescent individuals with high antibody titers and the lack of animal models to evaluate antibody efficacy.

Collaborating researchers from the Guangzhou Institute of Biomedicine and Health, the National Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, and the Guangzhou Laboratory have developed an experimental vaccine for HAdV-55 and immunized macaques. They used fluorescently labeled HAdV-55 virus particles as "bait" to isolate specific memory B cells from immune blood. Utilizing single-cell PCR technology, they cloned and screened 9 strains of highly effective monoclonal neutralizing antibodies (IC50 < 1.0 ng/ml).

Using the HAdV-55 infection model (humanized receptor transgenic mice) and disease model (ferrets) established by the team in previous studies, the researchers confirmed that monoclonal neutralizing antibodies can effectively block HAdV-55 invasion and reduce the lung inflammation it causes. Further research revealed that monoclonal antibodies recognizing the virus Fiber protein could block the virus from binding to receptors, while those recognizing the Hexon protein could inhibit the virus from escaping the endosome.

The highly potent monoclonal neutralizing antibodies obtained in this study have the potential to be developed into therapeutic strategies against HAdV-55 infection, deepening our understanding of the mechanisms of adenovirus antibody action.

It is worth noting that neutralizing antibodies derived from immunized macaques are highly homologous to human antibodies. Previously, the research team successfully obtained monoclonal neutralizing antibodies against highly pathogenic avian influenza H5N1 in 2013 and Ebola virus in 2016 using immunized macaques. Therefore, based on immunized macaques and single-cell PCR technology, highly humanized neutralizing antibodies against newly emerging infectious diseases can be rapidly developed.

For more information, refer to the related paper: https://doi.org/10.1080/22221751.2024.2307513.