Asia-Pacific Biotech News

Broadly Neutralising Antibodies (bNAbs) as the Key to Longer-Lasting COVID-19 Vaccines

A study in Japan has identified bNAbs from long-term COVID-19 patients that can better protect against evolving SARS-CoV-2 strains.

COVID-19 started with just one original SARS-CoV-2 variant. Over time, the virus accumulates genetic mutations that outsmart our immune system, leading to the rise of new variants that increase its chances of successful infection. Simultaneously, our body counters the invading pathogens by producing antibodies that can prevent viral entry into the cells. While antibodies are usually thought to be highly specific in what they can neutralise, there is an elite group of antibodies that are less well known: Broadly Neutralising Antibodies (bNAbs). Unlike non-bNAbs, bNAbs are unique as they target structures in the virus that are conserved even with mutations. Hence, even if the virus mutates, the conserved structure will still exist, and the immune system can neutralise it.

Unfortunately, the nascent field of bNAbs and its accompanying uncertainties mean that it is not at the forefront of COVID-19 research. However, with the current SARS-CoV-2 variant landscape being dominated by the Omicron lineage—variants that are characterised by breakthrough infections and reinfections—scientists are turning to bNAbs to improve vaccine potency. Pioneering this work is a team of scientists from Hiroshima University. Led by Professor Tomoharu Yasuda of the Graduate School of Biomedical Health Sciences, the team published their findings in Communications Biology.  

To identify bNABs that are effective against SARS-CoV-2 variants, the researchers tested sera from recuperating non-vaccinated COVID-19 patients over the course of 55 days. They noticed a surge in neutralising antibodies starting 17 days after diagnosis, with the highest frequency of bnAbs on day 55.  

After analysing the samples, the researchers identified four monoclonal antibodies (mAbs)—antibodies made in the laboratory that can mimic natural antibodies—which can neutralise all variants of SARS-CoV-2 to varying degrees. Out of these four monoclonal antibodies, NCV2SG48 showed great promise as it was able to neutralise all SARS-CoV-2 variants, including the highly infectious Omicron variants and the deadly Delta variants. However, a relatively high concentration of NCV2SG48 is required to render it effective against SARS-CoV-2 variants. This may pose problems in therapeutic applications as mAbs are meant to be present in low concentrations in vaccines to increase vaccine efficacy, increase immune memory, and limit potential adverse effects.  

To counter this problem, the authors mixed NCV2SG48 with another mAb that is able to neutralise all variants except Beta and Omicron and has a lower concentration threshold for effectiveness. They found that the antibodies do not obstruct each other and are able to broadly neutralise all the variants tested. Hence, a cocktail of the two monoclonal bNAbs is an attractive treatment option to target the broadness of the variant spectrum and maximise effectiveness at a low dose.

In addition, the authors were able to elucidate the mechanism behind the potency of bNAbs. Analysing their structure via X-ray scans, the authors noticed that prolonged exposure to SARS-CoV-2 triggers a change in the structure of NCV2SG48, which equips it with an extensive binding interface. This means that NCV2SG48 can not only block the targeted conserved structures of the virus like normal antibodies, but the neighbouring structures as well. Hence, NCV2SG48 prevents viral entry into the cells by effectively covering almost the entire viral surface.

Interestingly, the isolated bnAbs came from elderly patients, an age group conventionally accepted to be at a higher risk of serious symptoms and death. Thus, the authors believe there may be a correlation between the ability to generate neutralising antibodies and clinical outcomes in the elderly. Regardless, the authors hope that their study can contribute to the development of more effective vaccines and therapeutics against SARS-CoV-2 variants. [APBN]

Source: Shitaoka et al. (2023). Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants. Communications Biology, 6(1), 395. https://doi.org/10.1038/s42003-023-04782-6