Is the Influenza B/Yamagata Virus Now Extinct?

What made the latest influenza vaccine recommendations so interesting from years past was the exclusion of B/Yamagata viruses in the vaccine protection.

Image credit: Sanofi

In March, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) met to discuss and make recommendations on the vaccine viruses for US flu vaccines for the 2024-2025 flu season. The Committee recommended that all 2024-2025 US flu vaccines be 3-component (trivalent) vaccines and include an influenza A(H1N1), an A(H3N2) and a B/Victoria-lineage vaccine virus.¹

What made these new recommendations so interesting from years past was the exclusion of vaccine protection against B/Yamagata viruses, because this group of viruses is no longer actively circulating. As such, the recommendation was to omit quadrivalent protection in favor of trivalent protection.

“FDA has been engaging and interacting with manufacturers of FDA-approved seasonal flu vaccines and providing scientific and regulatory advice to them to facilitate the timely availability of approved safe and effective trivalent seasonal flu vaccines for the 2024-2025 US flu season,” FDA wrote in a statement.¹

The World Health Organization also weighed in and offered its specific recommendations for the upcoming season, including the following:

Egg-based vaccines

• an A/Victoria/4897/2022 (H1N1)pdm09-like virus;
• an A/Thailand/8/2022 (H3N2)-like virus; and
• a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.²

Cell culture- or recombinant-based vaccines

• an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;
• an A/Massachusetts/18/2022 (H3N2)-like virus; and
• a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.²

The Rise and Fall of Viruses
In the early 1980s, the influenza B viruses split into 2 lineages, becoming the B/Victoria and B/Yamagata viruses. These 2 lineages showed distinct antigenicity and transmission dynamics and have co-circulated during each influenza season since 2001.³

And the now perceived extinction of this B/Yamagata viruses reminds everyone of the enigmatic nature of viruses and how they can be omnipresent in a moment in time and then disappear from circulation.

Interestingly, COVID-19 is believed to be a primary factor in the possible extinction.

The COVID-19 pandemic and the public health measures that were put in place to contain the spread of SARS-CoV-2, caused major disruptions to the circulation of influenza and other respiratory viruses.⁴

Evidence of the Extinction
In learning more about the possible extinction of Influenza B/Yamagata virus, a group of investigators performed a systematic review utilizing multiple complementary sources of information looking at databases relevant articles published in PubMed and Embase, and data from the FluNet, Global Initiative on Sharing All Influenza Data, and GenBank databases, webpages of respiratory virus surveillance systems from countries worldwide, and the Global Influenza Hospital Surveillance Network.⁵

Their study was published in The Lancet Microbe.

“A progressive decline of influenza B/Yamagata detections was reported across all sources, in absolute terms (total number of cases), as positivity rate, and as a proportion of influenza B detections,” the investigators wrote.⁵

They point out that predictions are difficult to make, but the significant decrease of influenza B/Yamagata points to the possibility.

“Globally, during 2012–17, B/Yamagata viruses caused a larger proportion of infections than B/Victoria viruses, but in the 2 years before the COVID-19 pandemic, the B/Victoria lineage had become largely prevalent, with the B/Yamagata-to-B/Victoria ratio dropping to 1:4·5 in 2018 and 1:19·3 in 2019,” The investigators wrote. “Early in the course of the COVID-19 pandemic (ie, from March, 2020), and even after influenza viruses started circulating again in late 2021, B/Yamagata lineage viruses were detected in only a few countries globally, thereby giving rise to the question as to whether B/Yamagata lineage viruses were on the verge of extinction.”

Vaccine Availability
No matter what the true determination of the B/Yamagata status is, in terms of protection for the upcoming respiratory virus season, which begins in just a few months, the federal government says there will be enough influenza vaccines for the season.

“FDA anticipates that there will be an adequate and diverse supply of approved trivalent seasonal flu vaccines for the United States in the coming season,” the FDA statement said.

References
1. US Will Transition to Trivalent Flu Vaccines for 2024-2025. Centers for Disease Control and Prevention (CDC). March 8, 2024. Accessed May 20,2024.
https://www.cdc.gov/flu/spotlights/2023-2024/trivalent-vaccines-2024-2025.htm
2. Recommended composition of influenza virus vaccines for use in the 2024-2025 northern hemisphere influenza season. WHO. February 23, 2024. Accessed May 20,2024.
https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2024-2025-northern-hemisphere-influenza-season
3. Yang J, Lau YC, Wu P, Feng L, Wang X, Chen T, Ali ST, Peng Z, Fang VJ, Zhang J, He Y, Lau EHY, Qin Y, Yang J, Zheng J, Jiang H, Yu H, Cowling BJ. Variation in Influenza B Virus Epidemiology by Lineage, China. Emerg Infect Dis. 2018 Aug;24(8):1536-1540. doi: 10.3201/eid2408.180063. PMID: 30015611; PMCID: PMC6056115.
4. Dhanasekaran V, Sullivan S, Edwards KM, et al. Human seasonal influenza under COVID-19 and the potential consequences of influenza lineage elimination. Nat Commun. 2022;13(1):1721. Published 2022 Mar 31.
doi:10.1038/s41467-022-29402-5
5. Caini S, Meijer A, Nunes MC, et al. Probable extinction of influenza B/Yamagata and its public health implications: a systematic literature review and assessment of global surveillance databases. Lancet Microbe. Published online May 7, 2024. doi:10.1016/S2666-5247(24)00066-1