Marilyn Bulloch, PharmD, BCPS, FCCM

A version of this article as originally published by PharmacyTimes.com.

The 2020-2021 influenza season was strikingly quiet. Cumulative positivity between September 27, 2020 and May 15, 2021 was 0.2%, a rate substantially lower than the 17% average positivity for the 3 previous seasons.

 Although some have argued that positive tests were reduced due to a lack of testing, testing for influenza in North America was consistent with previous years.

 More likely, the low infection rate is the credit of a combination of social distancing, face masks, and vaccinations.

Although the virus did not pose its usual seasonal burden, it was not eradicated. The dominant circulating influenza virus varied worldwide. In the United States, tests conducted by clinical laboratories indicate that Influenza B accounted for approximately two-thirds of infections.

 Influenza B was also dominant in China and the Middle East, while Influenza A appeared to be predominate in North Korea and Japan.

When the flu season for the northern hemisphere ends in spring, it begins for the southern hemisphere and runs through September. The southern hemisphere season is considered to precede the northern hemisphere and provided valuable insight on what to expect when flu season returns in October. The southern hemisphere, so far, is also experiencing a substantially calm flu season.

 Although clinically this may sound positive, it also makes preparing for the next flu season in the northern hemisphere more difficult.

With fewer virus specimens, experts say that it is more difficult to identify and characterize the full extent of the circulating influenza viruses’ genetic and antigenic diversity. In animals, the southern hemisphere’s 2021 vaccines have had mixed efficacy in producing antisera that recognizes, and subsequently affords protection against, circulating viruses.

 Though the match in these models seems to be stronger with the Influenza B lineages and circulating strains, there is more inconsistent efficacy with the Influenza A composition. In fact, changes in circulating Influenza A viruses, especially H3N2 strains, led experts to recommend changes to the composition of the 2021-2022 vaccine for the northern hemisphere.

The recommendations for influenza vaccine composition for Fall 2021 were released in February 2021 by the World Health Organization.

 For the second year in a row, the composition of the vaccine will depend on whether it is egg-based or cell-based or recombinant vaccine. However, the different compositions do not necessarily mean that there is a substantial difference in vaccine-produced immunity to circulating strains. According to the World Health Organization, not all viruses are optimal for the different production systems seen with egg-based vaccines versus cell or recombinant based vaccines. To accommodate this, different viruses with similar properties were selected as prototypes for timely vaccine production to ensure adequate supply by Fall 2021.

In 2021-2022, all influenza vaccines, regardless of type, will contain the same lineages of Influenza B, which are unchanged from the 2020-2021 season. This coincides with the matched protection seen in both the northern hemisphere’s 2020-2021 season and the southern hemisphere’s season so far. When lineage has been determined, most Influenza B viruses in 2020-2021 were B/Victoria/2/87 or B/Yamagata/16/88 lineage, which were closely related genetically and antigenically to the strains included in the vaccine. Quadrivalent vaccines will again include B/Washington/02/2019 (B/Victoria lineage)-like virus and B/Phuket/3073/2013 (B Yamagata lineage)-like virus. Trivalent vaccines will only contain the Victoria lineage, but the majority of available vaccines in the United States have transitioned to a quadrivalent composition.

Both strains of Influenza A for the northern hemisphere vaccines will be different from those included last season. Unlike last flu season, they will only differ by the H1N1 component rather than both strains of Influenza A. The H1N1 composition will resemble the current southern hemisphere vaccines’ H1N1 composition. Vaccines that are egg-based will include A/Victoria/2570/2019(H1N1)pdm09-like virus while cell and recombinant-based vaccines will include A/Wisconsin/588/2019 (H1N1)pdm09-like virus. The southern hemisphere’s current H3N2 component (Influenza A/Hong Kong/ 45/2019 (H3N2)-like virus in cell or recombinant-based vaccines and A/Hong Kong/2671/2019 (H3N2)-like virus) is identical to what was included in the northern hemisphere’s vaccines for 2020-2021, but appear to be producing inconsistent efficacy and protection to current circulating strains. As a result, vaccines administered in the fall will contain an updated strain of H3N2, an A/Cambodia/e0826360/2020 (H3N2)-like virus.

It is impossible to predict if the low rates of influenza in the 2020-2021 season will be repeated or serve as an isolated anomaly. The impact of the change in vaccine composition will not be known for almost another year. Eased infection control practices related to COVID-19, such as reduced face mask wearing, will also likely return influenza transmission to its usual potential. Although these measures had a noticeable contribution to the decrease in transmission of the influenza virus, the influenza vaccine remains the best way to protect against the potentially fatal virus.

It is important that patients be encouraged to receive the vaccine, even if Influenza B continues to dominate in the upcoming season, since there is a post-vaccination decline in protective antibodies. This past year has introduced the possibility that influenza season does not have to consistently produce a high health burden. The prevention strategies championed by pharmacists and other health care providers for years, vaccination and practical infection prevention practices demonstrated their capabilities in full force. While it is unlikely that all of the practices employed during the 2020-2021 season for the COVID-19 pandemic will be broadly utilized during future flu seasons, pharmacists can and should continue to champion common-sense preventative strategies such as hand hygiene, staying home when sick, and most importantly, annual influenza vaccination.

World Health Organization. Recommended composition of influenza-virus vaccines for use in the 2021-2022 northern hemisphere influenza season. Updated February 26, 2021. Accessed May 25, 2021. 

https://www.who.int/influenza/vaccines/virus/recommendations/2021-22_north/en/

Centers for Disease Control and Prevention. FluView. Updated May 15, 2021. Accessed May 25, 2021. 

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Both strains of Influenza A will be different from those included the northern hemisphere's last season.

Vaccination Updates for the 2021-2022 Flu Season

When the CDC announced changes to the 2019-20

vaccine in the spring of 2019, it was with the anticipation that the vaccine would be a much better match to the influenza virus than it has been in the past few seasons.

Vaccines for the 2019-2020 Northern Hemisphere saw updates to both the H3N2 and H1N1 influenza A strains, which had not been updated in a couple of years.

Additionally, all regular-dose and recombinant vaccines are now quadrivalent and therefore covering both lineages of influenza B.

The CDC still continues to recommend that vaccination be offered by the end of October.

The recommendations for the CDC 2019-2020 quadrivalent influenza vaccine are:

A/Brisbane/02/2018 (H1N1)pdm09-like virus

B/Colorado/06/2017-like virus (Victoria lineage)

B/Phuket/3073/2013-like virus (Yamagata lineage)

However, a few indicators raise the question about if the vaccine really is as well matched as was anticipated. The influenza season in the Southern Hemisphere generally lasts from April to September and precedes the northern hemisphere’s season. As a result, trends in vaccine effectiveness and influenza infection in the Southern Hemisphere may give clinicians in the Northern Hemisphere potential clues about what to expect.

A recent study indicates that there was an antigenic mismatch of the 2019 Southern Hemisphere influenza vaccine within the H3N2 component.

The H3N2 strain A/Switzerland/8060/2017 was recommended for their seasonal vaccine in 2019. Unfortunately, the strain was ultimately found to have a substitution that results in the loss of a glycosylation site in the antigenic site B of hemagglutinin which is associated with low vaccine effectiveness during H3N2-dominated influenza seasons.

A version of this article was originally published by Pharmacy Times. Visit

Marilyn Bulloch, PharmD, BCPS, FCCM

Articles

Vaccination Updates for the 2021-2022 Flu Season

Uncertainty Remains in the 2019-2020 Flu Vaccine Match