Different antibodies serve distinct functions in the human body, and IgA antibodies, in particular, play a crucial role in the adaptive immune system. Naturally residing in the mucosal membranes of the airways, IgA antibodies are essential for defending against respiratory infections. Low levels or absence of mucosal IgA have been associated with an increased risk of breakthrough infections caused by SARS-CoV-2.
Challenges with current vaccines
Traditional COVID-19 vaccines primarily stimulate the production of IgG antibodies within the body. However, earlier studies have revealed limitations in their effectiveness against the new Omicron variants of the virus. This raised the need for alternative strategies to bolster protection against evolving viral threats.
To address this challenge, a research group led by Professor Qiang Pan-Hammarström at the Karolinska Institutet employed genetic engineering techniques to create IgA antibodies with a similar binding mechanism to IgG antibodies.
In experiments involving mice infected with the Omicron variant, the IgA antibody treatment was administered via nasal drops. The results were promising, as the nasal drops significantly reduced the virus load in the trachea and lungs of the infected mice. Importantly, the IgA antibodies exhibited stronger binding to the SARS-CoV-2 spike protein and demonstrated superior virus-neutralizing capabilities compared to the original IgG antibodies.
Complementary approach, not a replacement
Professor Harold Marcotte, associate professor at the Department of Medical Biochemistry and Biophysics at the Karolinska Institutet and the first author of the study, emphasized that these genetically engineered antibodies are not intended to replace current vaccines. Rather, they offer a complementary approach to passive immunization. This approach holds promise for safeguarding vulnerable individuals, such as the elderly or immunocompromised persons.
Researchers have high hopes that this method can be adapted to neutralize other current and emerging variants of the virus. Beyond COVID-19, this approach shows potential in addressing various infectious diseases, including influenza and other respiratory infections, as well as gastric mucosal infections like Helicobacter pylori, where vaccines are currently unavailable.
This study was conducted within the European research consortium ATAC and involved collaborative efforts between Sweden and China, including institutions such as Linköping University, Peking University, Guangzhou Institutes of Biomedicine and Health, Fudan University, Peking Union Medical College, Wuhan Institute of Virology, and Kunming Institute of Zoology.
Funding was provided by the EU's Horizon 2020 research and innovation program, a joint VR-NCSF funding initiative, the Knut and Alice Wallenberg Foundation, and a Swiss National Science Foundation grant (BRIDGE). Additionally, some of the authors are listed as inventors of patents related to antibody treatment.