Preprint: Cross-Reactive Human Antibody Responses to H5N1 Influenza Virus Neuraminidase are Shaped by Immune History
Preprint: Neuraminidase Imprinting and the Age-related Risk of Zoonotic Influenza
Simply put, the first influenza virus you are exposed to (HA Group 1 or 2) is believed to affect your immune response for the rest of your life (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression).
How much real-world protection early or past H1/H2 exposure might offer against H5Nx - or how long it might last - are unknown, but it has been suggested it might provide an `edge' against severe disease.
Given the challenges of quickly bringing a safe, and effective, H5N1 vaccine to the masses (see SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1), there is understandably a lot of interest in potential stop-gap measures that might help blunt the opening months of a pandemic.
So far, boosting with existing H1N1 vaccines has shown very limited value (see EID Journal: Investigation of Influenza A(H5N1) Virus Neutralization by Quadrivalent Seasonal Vaccines, United Kingdom, 2021–2024).
But today we have a study which suggests using an interesting - but potentially controversial - option; deploying a standalone booster ASO3 adjuvanted H1N1 vaccine, similar to the one used in Europe during the 2009 pandemic.
Given its highly publicized link to an increased incidence of narcolepsy - particularly in children and adolescents (see Finland: Task Force Report On Pandemrix-Narcolepsy Link) - an ASO3 adjuvanted vaccine would likely face stiff headwinds from an already vaccine-hesitant society.
First, a link, and the abstract to the study - which contains some surprises - after which we'll take a deeper look into their findings.
Adjuvanted influenza vaccination increases pre-existing H5N1 cross-reactive antibodies
Mariana Alcocer Bonifaz, Disha Bhavsar, Claire-Anne Siegrist, Arnaud Didierlaurent & Benjamin Meyer
Published: 07 January 2026article number , (2026)Download PDF
Abstract
Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic. Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States. These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies.In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodies.
Additionally, we find that AS03-adjuvanted pandemic H1N1 vaccination increases H5N1 cross-reactive antibodies significantly in a pandemic H1N1 immunologically partially naïve population. Furthermore, we show that immune imprinting causes distinct H5N1 cross-reactive antibody patterns pre-vaccination.
(SNIP)
In conclusion, we could show that low levels of H5N1 cross-neutralizing antibodies exist in the population in 2009 and more recently in 2023. Low dose AS03-adjuvanted pandemic H1N1 vaccination was able to substantially induce H5N1 cross-reactive antibodies and could overcome the effect of immune imprinting on H5N1 cross-reactive antibody patterns in a pH1N1 immunologically partially naïve population.
In a nutshell, the authors report:
- Most adults carry weak antibodies against today's H5N1 bird flu from past human flu infections or vaccines, which may reduce the severity of infection.
- A low-dose AS03 adjuvanted H1N1 vaccine increases these antibodies nearly 4-fold - compared to just 30% from the standard seasonal flu shot.
- This effect would likely be of greatest benefit to those exposed to HA Group 2 viruses (H3N2) early in life, as HA Group 1 subjects saw less impact.
- In a bit of a twist, receipt of the regular seasonal flu shot within a few weeks of the booster actually dampened its effect.
It would be of interest to know if other adjuvants - like MF59 (widely used in Europe) - would produce similar gains. But in a severe enough pandemic, even an AS03 vaccine might be an attractive option.
As we've discussed previously (see Manufacturing Pandemic Flu Vaccines: Easier Said Than Done), producing and delivering billions of doses of a safe and effective H5 vaccine is a tall order, and success is not guaranteed.
Add in the growing anti-science bias of the public, often fueled by AI generated clickbait videos and political rhetoric, even a low CFR H5 pandemic could be disastrous.We've also seen warnings that our current influenza antivirals may be lacking (see St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk) along with signs of growing antiviral resistance in avian flu (see Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms).
While I could certainly do without another pandemic in my lifetime, nature's laboratory may have other plans.
