How is the influenza vaccine developed each year?

Seasonal influenza (flu) vaccines are designed each year to protect against the virus types most likely to spread and cause illness during the upcoming season. The components of the vaccine are selected based on:

• Which flu viruses are making people sick prior to the upcoming season and the extent to which they are spreading
• The ability of potential vaccine viruses to provide cross-protection against a range of related flu viruses
• How well the previous vaccines worked

There are over 140 National Influenza Centres in more than 110 countries conducting year-round surveillance for flu viruses. These centres receive and test thousands of flu virus samples as part of the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS).

A subset (10-20%) of all viruses received are selected for genetic sequencing and more detailed analysis. This sample includes viruses from particularly severe or fatal cases, those with potential antigenic variants and a general subset of circulating viruses.

Genetic analyses are carried out to identify the emergence of new virus groups, the degree to which they vary from related viruses and how the currently circulating viruses are evolving. Genetic mutations, leading to different amino acids at key sites on the virus may impact how the virus behaves, whether it makes people sick and how it reacts to vaccines. Collecting lots of data on these mutations makes it easier to predict in future which changes will be important to consider for vaccine development. Finding these patterns also helps with general surveillance efforts and monitoring variants.

Genomic analyses are also used to monitor whether viruses acquire mutations whilst being grown in the environments used to develop vaccines. This will also influence which components will be used in vaccine design. Updates sequence data are shared within GISRS and made publicly available via the GISAID EpiFlu database. Whole genome sequencing is particularly helpful in identifying animal viruses causing human infection as well as detecting reassortment events between co-circulating human or animal viruses.

The WHO vaccine composition committee presents global flu data and recommends specific vaccine viruses for trivalent (three-virus component) and quadrivalent (four-virus component) flu vaccines. Each country then makes its own decision on the viruses that will be included in flu vaccines they licence.

The current WHO recommendations for quadrivalent vaccines for use in the 2023 southern hemisphere influenza season contain the following:

Egg-based vaccines

• An A/Sydney/5/2021 (H1N1)pdm09-like virus;
• An A/Darwin/9/2021 (H3N2)-like virus;
• A B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and
• A B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

Cell culture- or recombinant-based vaccines

• An A/Sydney/5/2021 (H1N1)pdm09-like virus;
• An A/Darwin/6/2021 (H3N2)-like virus;
• A B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and
• A B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

WHO recommends that trivalent vaccines for use in the 2023 southern hemisphere influenza season contain the following:

Egg-based vaccines

• An A/Sydney/5/2021 (H1N1)pdm09-like virus;
• An A/Darwin/9/2021 (H3N2)-like virus; and
• A B/Austria/1359417/2021 (B/Victoria lineage)-like virus.

Cell culture- or recombinant-based vaccines

• An A/Sydney/5/2021 (H1N1)pdm09-like virus;
• An A/Darwin/6/2021 (H3N2)-like virus; and
• A B/Austria/1359417/2021 (B/Victoria lineage)-like virus

Click here to enlarge the image

Figure 1 – Diagram of the individual steps in the selection of candidate vaccine viruses and development of standardizing reagents for seasonal influenza and for a potential H5N1 influenza pandemic. For seasonal vaccines the timelines are: Steps 1–4: the collection, isolation and thorough antigenic and genetic characterization of recent virus isolates continues throughout the year; Step 4a: comparisons of the recognition of representative recent viruses by vaccine-induced antibodies in human sera are conducted 2–3 weeks before the biannual WHO vaccine consultation meetings; Steps 5, 6a and 7a: candidate viruses for vaccine use are reviewed and selected, and high-growth reassortants prepared and characterized following identification of (potential) antigenic variants– these steps are not solely dictated by the recommendations of the WHO biannual vaccine virus consultations. Step 8: Evaluation of their growth properties is conducted in a timely manner around the time of the WHO vaccine virus consultations and prior to authorization of vaccine composition by national authorities. Step 9a: Preparation of the standardizing reagents for new vaccine components is initiated once the particular vaccine virus has been selected following the WHO recommendation. Source: Influenza

Learn more about the Influza vaccine in this WHO Science in 5 podcast episode

References

Selecting Viruses for the Seasonal Influenza Vaccine

Improving influenza vaccine virus selectionReport of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14–16 June 2010

New recommendations for the composition of influenza vaccines in 2023 for the southern hemisphere