Latest research from the National Institute for Biological Standards and Control (NIBSC) shows that a novel antibody-based approach may be effective at protecting against pandemic influenza.
In a recent study published in the journal Frontiers in Immunology, scientists investigated the use of gene therapy to deliver a special type of antibody fragment isolated from alpacas, called a single domain antibody or nanobody. They demonstrated that the nanobodies offered safe and long-lasting protection against multiple strains of influenza virus in mice.
In contrast to previous reports, the scientists were able to show that the nanobodies protect against influenza without activating the immune system – a finding that has important implications for the future design of safe antibody-based therapies.
Influenza remains a major challenge for public health worldwide. While vaccines are available, their effectiveness is limited in certain patient groups meaning there is an urgent need to develop alternative strategies.
Antibody gene therapy represents a promising novel solution as it would enable the sustained production of an antibody within an individual over the long-term. Single domain antibodies, also known as nanobodies, are particularly well suited to gene therapy due to their small size and simple structure. This type of antibody is unique to camelid species such as alpacas and can be isolated from immunised animals.
The team of scientists at the NIBSC had already established that a nanobody named R1a-B6 shows broad neutralising activity against influenza in vitro. In their latest study, they aimed to further investigate the effectiveness of this nanobody in vivo.
The gene encoding the nanobody was first inserted into an Adeno-Associated virus (AVV) vector and delivered to mice via an intramuscular injection. This method of delivery led to much higher expression levels than those previously reported for intranasal delivery and the levels of expression remained stable over the 24-week observation period.
The scientists were then able to show that mice that had received the gene therapy were completely protected against the lethal effects of the H1N1 and H5N1 influenza strains.
In order to increase the retention of the small nanobody in the circulation, it was fused to an antibody Fc domain. This domain is also involved in activating the host immune response but, surprisingly, this did not appear to contribute to the protective effect of the nanobody. Instead, it is likely that the nanobody protected against influenza solely by inhibiting viral membrane fusion and blocking entry into the host cell.
Altogether, this research demonstrates that nanobody-based gene therapy is a viable strategy against influenza and paves the way for further optimisation of nanobody design and delivery.
Dr Simon Hufton, who led this study comments that:
“Our findings have implications for developing optimum antibody formats and delivery options to provide safe, long term protection from influenza in preparation for future pandemics. This may be particularly useful for protecting vulnerable groups who may not be able to adequately respond to vaccination in a pandemic emergency”
Going forward, this approach could be expanded beyond influenza to help protect against other infectious diseases. For example, attempts to isolate nanobodies against the SARS-CoV-2 virus responsible for COVID-19 are currently underway.
Further information about our nanobody research can be found here.