BSL-3 – Credit CDC PHIL
#18,592
Although a handful of countries have arranged to purchase a limited quantity of H5Nx vaccine (see here, here, here, and here) - existing vaccines may not be a good match against any emerging `pandemic strain' of H5 - and even a well-matched vaccine might only provide limited protection against severe disease.
Given the difficulties of mass producing (and deploying) billions of doses of a pandemic flu shot (see Manufacturing Pandemic Flu Vaccines: Easier Said Than Done), most people won't be offered a flu jab during the first year (see Referral: SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1).
While there are antivirals like Oseltamivir (aka Tamiflu), I.V. Peramavir, and the newer Baloxavir, all are in limited supply, must be administered early in the course of an illness, and - at best - can only reduce the severity and duration of symptoms (Clinical Inf. Dis.: Benefit of Early Oseltamivir Therapy for Adults Hospitalized with Influenza A: An Observational Study).
Add in the potential for (spontaneous or acquired) resistance, and the fact that we've had problems distributing these type of drugs during moderate-to-severe flu seasons, and it is easy to see why other approaches are needed.
During the COVID pandemic a third option - monoclonal antibodies (mAbs) - were introduced late in 2020, and gained wider use in 2021. For a time they were hailed as `game changers', but within a couple of years all had been rendered ineffective by changes to the virus (see FDA Withdraws EUA (Emergency Use Authorization) For Last COVID Monoclonal Antibody: Bebtelovimab).
Still, since mAbs can be used both as a treatment and a (short-term) prophylaxis, the could be quite handy during the opening months of any novel flu outbreak. Front line personnel could potentially receive it as a preventative measure, and those critically ill might be treated with it (along with antivirals).
One of the human mAbs that has been under investigation for years is MEDI8852, which binds to the HA gene of influenza A, allowing it to neutralize a broad spectrum of subtypes (see 2017's J.I.D. The Hemagglutinin A Stem Antibody MEDI8852 Prevents and Controls Disease and Limits Transmission of Pandemic Influenza Viruses).
Yesterday a research article was published in the Journal Science which detailed experiments performed at the University of Pittsburgh with MEDI8852 in preventing HPAI H5 infection in Macaques. While most of this report is behind a pay wall, the University of Pittsburgh has published a summary press release.
First, the link to the report, followed by excerpts from the press release. I'll have a bit more after the break:
Pre-exposure antibody prophylaxis protects macaques from severe influenza
Masaru Kanekiyo , Rebecca A. Gillespie , Kristine Cooper, Vanessa Guerra Canedo , Priscila M. S. Castanha, Amarendra Pegu, Eun Sung Yang , Luke Treaster, Gabin Yun, [...], and Simon M. Barratt-Boyes +26 authorsAuthors Info & Affiliations
Science 30 Jan 2025 Vol 387, Issue 6733 pp. 534-541
Antibody Treatment Prevents Severe Bird Flu in Monkeys
Anastasia (Ana) Gorelova
1/30/2025
PITTSBURGH – A prophylactic antibody-based immune therapy protects monkeys against severe disease caused by H5N1 avian flu, University of Pittsburgh and NIH Vaccine Research Center researchers report today in Science.
The broadly neutralizing antibody, which recognizes a relatively stable region of the bird flu virus, is less prone to losing its efficacy than antibodies targeting influenza’s more mutation-prone structures. This feature ensures that the immune protection can withstand the possible emergence of virus variants, akin to the SARS-CoV-2 mutants that evolved during the COVID-19 pandemic, and provide lasting protection against a globally spreading airborne infection.
“This type of prevention can be very useful in controlling infection outbreaks and containing the bird flu pandemic,” said co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at Pitt’s School of Medicine and the Center for Vaccine Research. “In our testing, the antibody performed beautifully. The antibody could be useful as a prophylactic of severe disease in vulnerable populations, and it also helped us establish the testing threshold for antibody levels in blood, which would be useful for judging the immune protection generated by a universal flu vaccine.”
(SNIP)
“This antibody is targeting a region that does not vary across different influenza viruses,” said co-corresponding author Simon Barratt-Boyes, Ph.D., professor of infectious diseases and microbiology at Pitt’s School of Public Health and immunology at Pitt’s School of Medicine. “Think about it as a tree – different species have different leaves and crowns, but tree trunks look very much the same. Similarly, the stalk region of the bird flu virus closely resembles the same structure of seasonal influenza, which makes it possible for stalk-targeting antibodies to provide universal protection.”
In a new study, monkeys pre-treated with a moderate dose of a broadly neutralizing MEDI8852 antibody were universally protected against severe disease and death. In addition to confirming the antibody’s efficacy in preventing serious adverse health outcomes, scientists were also able to establish its minimum serum concentration required for protection – a measurement useful for establishing the protective threshold of a potential universal flu vaccine.
The research sets the stage for the development of medical countermeasures against future influenza virus pandemics. Serum levels of MEDI8852 sufficient for protection remained stable for 8 to 12 weeks, suggesting that, if given early, it could protect first responders and others caring for patients at the beginning of an outbreak of H5N1.
Masaru Kanekiyo, Ph.D., of the NIH Vaccine Research Center, also contributed to the study. Other authors of this research are affiliated with the NIH Vaccine Research Center, Pitt, UPMC, University of Georgia and AstraZeneca.
This research was supported by the Vaccine Research Center, an intramural division of the National Institute of Allergy and Infectious Diseases; and the National Institute of Allergy and Infectious Diseases (grants, R01AI154894 and UC7AI180311, and contracts 75N93021C00014 and HHSN261201500003)
Although animal studies have been promising, MEDI8852 remains an investigational drug, and has not been approved for clinical use. It could be employed during a pandemic under an EUA (Emergency Use Authorization), as were the COVID mAbs.
While we have some existing pharmacological options for treating and preventing novel flu, none are particularly robust.
- Vaccines and mAbs may reduce the severity of illness, but many breakthrough infections are still expected.
- Antivirals - if given early enough - may reduce the severity and duration of symptoms, and may improve survival rates of some people. But are far from being a `cure'.
- All of these drugs may have (usually mild or moderate) adverse effects (AEs), that may discourage their use.
- And timely access to these drugs - even in high resource regions - is likely to be a problem. For the rest of the world, highly unlikely.
