Late yesterday the CDC published their weekly update on their H5N1 Bird Flu response, including a brief summary of their population immunity studies on the clade 2.3.4.4b H5N1 virus. While not unexpected, they report finding extremely low to no population immunity, even among those who recently received a seasonal flu vaccine.
Last December we saw some speculation that the seasonal flu shot might provide some limited protection, since the the NA (neuraminidase) gene segment in our seasonal H1N1 virus is antigenically similar to the NA gene segment in the clade 2.3.4.4b H5N1 virus.
In last month's Nature Dispatch: Risk Assessment On HPAI H5N1 From Mink, the authors also offered that: While different influenza A virus subtypes are antigenically distinct, some degree of cross-protection against H5N1 may be conferred by prior exposure to these seasonal strains, especially against the N1 neuraminidase.
And while admittedly somewhat anecdotal, we've observed a distinct age shift among H5N1 cases over the years, suggesting some degree of immunity may persist in those born before 1968, although it isn't clear whether that still applies with this clade.
While it is possible that some vestiges of cross-immunity may still exist, it would probably have relatively little impact should this virus acquire the ability to spread efficiently between humans.
The CDC does offer out the hope that antivirals remain effective and two existing candidate vaccine viruses (CVVs) would offer good cross-protection against A(H5N1) cattle outbreak viruses.But there are known limitations to both, which we'll look at briefly after the break.
CDC update
June 14, 2024 – CDC continues to respond to the public health challenge posed by a multistate outbreak of avian influenza A(H5N1) virus, or "A(H5N1) virus," in dairy cows and other animals in the United States. CDC is working in collaboration with the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), state public health and animal health officials, and other partners using a One Health approach.To date, there have been 3 human cases associated with an ongoing multistate outbreak of A(H5N1) in U.S. dairy cows. A Based on the information available at this time, CDC's current A(H5N1) bird flu human health risk assessment for the U.S. general public remains low. All three sporadic cases had direct contact with infected cows. On the animal health side, USDA is reporting that 92 dairy cow herds in 12 U.S. states have confirmed cases of A(H5N1) virus infections in dairy cows as the number of infected herds continues to grow.
Among other activities previously reported in past spotlights and still ongoing, recent highlights of CDC's response to this include:
Finalizing flu serology studies to determine the population immunity among the U.S. general population to the A(H5N1) clade 2.3.3.4b viruses causing outbreaks among animals in the United States.
CDC analyzed sera (blood) collected from people of all ages in all 10 HHS regions. Blood samples were collected during the 2022-2023 and 2021-2022 flu seasons. These samples were challenged with H5N1 virus to see whether there was an antibody reaction.Data from this study suggest that there is extremely low to no population immunity to clade 2.3.4.4b A(H5N1) viruses in the United States. Antibody levels remained low regardless of whether or not the participants had gotten a seasonal flu vaccination, meaning that seasonal flu vaccination did not produce antibodies to A(H5N1) viruses.
This means that there is little to no pre-existing immunity to this virus and most of the population would be susceptible to infection from this virus if it were to start infecting people easily and spreading from person-to-person. This finding is not unexpected because A(H5N1) viruses have not spread widely in people and are very different from current and recently circulating human seasonal influenza A viruses.
Earlier analyses have found that A(H5N1) viruses are susceptible to influenza antiviral medications and that two existing candidate vaccine viruses (CVVs) would offer good cross-protection against A(H5N1) cattle outbreak viruses.
- Continuing to support strategies to maximize protection of farm workers, who may be at higher risk for infection than others in the population.
- Continuing to support states that are monitoring people with exposure to cows, birds, or other domestic or wild animals infected, or potentially infected, with avian influenza A(H5N1) viruses. To date, more than 550 people have been monitored as a result of their exposure to infected or potentially infected animals, and at least 45 people who have developed flu-like symptoms have been tested as part of this targeted, situation-specific testing. Testing of exposed people who develop symptoms is happening at the state or local level, and CDC conducts confirmatory testing. More information on monitoring can be found at Symptom Monitoring Among Persons Exposed to HPAI.
- Continuing to monitor flu surveillance data using CDC's enhanced, nationwide summer surveillance strategy, especially in areas where A(H5N1) viruses have been detected in dairy cows or other animals for any unusual trends, including in flu-like illness, conjunctivitis, or influenza virus activity.Overall, for the most recent week of data, CDC flu surveillance systems show no indicators of unusual flu activity in people, including avian influenza A(H5N1) viruses.
While antivirals and vaccines would likely play a huge role in any influenza A pandemic, the devil is always in the details, and there are some substantial obstacles that would have to be overcome.
Influenza antivirals, like oseltamivir (Tamiflu®) and Baloxavir marboxil (trade name Xofluza®), can be lifesaving; particularly if administered in the first 48 hours of infection. But neither will cure the flu; as they only reduce the duration (and hopefully the severity) of infection.Stockpiles of both are limited, and we've seen repeated difficulties getting these medications into the hands of patients, even during seasonal flu epidemics (see CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir).
The more these drugs are used, the greater the chance of seeing resistant viruses emerge (see Antiviral Research: Antiviral susceptibility of clade 2.3.4.4b HPAI H5N1 Viruses Isolated From Birds & Mammals in the United States, 2022), and even without that happening, a small percentage of individuals receiving treatment will develop spontaneous resistance.
While antivirals can be extremely valuable, they do not guarantee a good outcome. Many avian flu patients over the years have succumbed despite receiving antiviral treatment.
As far as vaccines are concerned - even if the two existing CVVs `offer good cross-protection against A(H5N1) cattle outbreak viruses', they are unlikely to be the best match for any emerging H5N1 pandemic, and would only see limited use by high risk individuals early in a pandemic.
Early experimental H5 (and H7) avian flu vaccines have proved poorly immunogenic – requiring unusually large amounts of antigen (up to 12x normal).
Adding an adjuvant - spread across two shots several weeks apart - produced a much better immune response (see 2015's JAMA: Immune Response Of H7N9 Vaccine With & Without Adjuvant), but how well an increasingly vaccine skeptical population will accept an adjuvanted vaccine remains to be seen.
Additionally, we've seen problems manufacturing H5N1 vaccine in bulk (see 2019's Manufacturing Pandemic Flu Vaccines: Easier Said Than Done), particularly in egg-based production facilities.
Even under the most optimistic scenarios, most people will have to wait at least six to twelve months for a vaccine. And a 50% effective vaccine would be considered a `win'.
The bottom line is, despite having these tools, anything we can reasonably do today to prevent an H5N1 pandemic is probably worth the effort.
