By: Joo Hee Kwon, Pharm.D. Candidate c/o 2013
There are 3 antigenic types of influenza: A, B, and C. Influenza C causes mild illness and therefore does not cause epidemics. In contrast, influenza A and B are capable of causing mild to severe flu and in some cases death. An epidemic can occur depending on the number of people who are vaccinated, the predominant viruses of the season, and how the vaccines correlate with circulating strains during any given season.1 The most recent surveillance shows that the percentage of mortality due to pneumonia and influenza (6.1%) is below the epidemic threshold (7.5%).2
Influenza A can be classified based on two different types of surface proteins, hemagglutinin (H) and neuraminidase (N), and can be further divided into different strains. Influenza B does not have these subtypes, but just different strains. To differentiate among circulating viruses, influenza virus is named with the following details: antigenic type, host of origin, place of origin, strain number, and year of discovery, and if type A, the H and N numbers.3
Unlike other viruses, influenza virus strains change often as they mutate to adapt to the human immune response.4 When choosing the strains for each influenza season, the following are considered: what viruses exist, how prevalent they are, and the degree of virulence in causing clinical illness. After this process is completed by the World Health Organization’s (WHO) surveillance system, U.S. FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) will decide in February (prior to the next influenza season) whether to follow or change their recommendations5, and as soon as the decision is announced, the manufacturers will start developing the vaccines, which usually takes at least 6 months.6
According to human serology tests performed by WHO Global Influenza Surveillance and Response System (GISRS), the strains for 2012-2013 season in northern hemisphere are A/California/7/2009 (H1N1) pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; and a B/Wisconsin/1/2010-like virus (B/Yamagata lineage). Only the first of these strains is the same as last season. The other 2 strains from previous season that changed are A/Perth/16/2009(H3N2)-like virus and B/Brisbane/60/2008-like virus (B/Victoria lineage).7
According to the recent meeting minutes from VRBPAC, vaccines will include all of the above strains as well as B/Brisbane/60/2008-like virus, following the WHO recommendation to include this specific strain if the country is considering two influenza B viruses in vaccines.5, 8 The reason for inclusion of 2 influenza B viruses is that both B/Yamagata and B/Victoria lineages circulated in different parts of the world at the same time. B/Victoria was the strain of choice over the past two seasons due to its higher prevalence; however, infections from B/Yamagata strain were also witnessed during the 2011-12 season and both strains are different enough to offer cross-protection. Hence, the B/Yamagata was also chosen for the upcoming season.9 Among the B/Yamagata viruses, B/Wisconsin/1/2010-like virus was selected since most of the viruses of this lineage were similar to this specific virus both genetically and antigenically. Similarly, A/Victoria/361/2011 (H3N2)-like virus was chosen for the next season based on human serology study results, which showed more antibody titer against this strain in comparison to the previously chosen strain A/Perth/16/2009.7
Vaccines render protection by causing the formation of antibodies against the specific virus strains included in the vaccine. This process takes about two weeks from the time of vaccination. There are generally two types of vaccines: the flu shot and the Live Attenuated Influenza Vaccine (LAIV) nasal spray. The flu shot contains inactivated or killed vaccine. There are intramuscular flu shots, which are indicated for people aged 6 months and older, the Fluzone High-Dose shot for patients 65 years and older, and the Fluzone Intradermal shot for patients 18—64 years old.10 Fluzone High-Dose contains four times the amount of antigen as that in the regular flu shot, making this vaccine suitable for the elderly as their immunity is weakened with age and higher doses of the vaccine are needed to build adequate immunity to the flu.11 The nasal spray flu vaccine that contains weakened live virus is only indicated for healthy people aged 2—49 years.10
Everyone over 6 months of age can be vaccinated against the flu; however, vaccination is contraindicated in people who are allergic to chicken eggs or any other component of the vaccines, people with moderate to severe illness with fever, and those with history of Guillain-Barré Syndrome that occurred after vaccination and without risk factors for flu complications.10 In addition, the nasal spray flu vaccine cannot be given to pregnant women, those with a weakened immune system or asthma, children younger than 5 years old who had at least one wheezing episode within previous year, people with severe nasal condition that makes breathing difficult, and children or adolescents on long-term aspirin treatment.12
Most of the vaccines available for the 2012-13 flu season are trivalent. This February, the FDA approved FluMist Quadrivalent, the first LAIV to include the 2 influenza B viruses, one of which was chosen for the upcoming season. It is a nasal spray formulation that is made the same way as the trivalent FluMist vaccine by the same manufacturer MedImmune LLC.9 FluMist Quadrivalent gives added protection as it protects against one more strain of influenza B virus.
When a virus of a non-human origin affects humans, that virus is called a variant virus. The variant virus results from a combination of genes from human, swine, and avian as well as other influenza viruses. In 2011, a variant of the influenza A H3N2 virus or “swine flu” that normally infects pigs began to cause influenza illness in humans. The number of H3N2 variant cases has increased partly due to enhanced surveillance programs and quite possibly an increased incidence of cases. There were several case reports of H3N2 variant virus infections since last October. Twelve people from August through December of 2011 were infected with A(H3N2)v in Indiana, Iowa, Maine, Pennsylvania, and West Virginia. Six of these people did not have swine exposure and 11 were children. All patients recovered without complications.13 In April 2012, one child in Utah was reported to be infected with the same type of virus that has the M gene from A(H1N1)2009 virus; the child recovered fully after treatment with oseltamivir.14
The virus can become a pandemic if a major change occurs in the genetic design of H3N2, which can happen if the human virus transmits across multiple, different species. People at high risk of acquiring such infection are those living or working in close proximity to pigs. The virus can be spread among humans the same way other viruses do: through contacting air droplets from an infected person when coughing or sneezing. Medications to treat the variant influenza virus are similar to the treatment for other types of influenza: amantadine, rimantadine, oseltamivir and zanamivir; but, amantadine and rimantadine are not suggested for use due to the concern for resistance.15 Currently, a vaccine that will give protection against this variant virus is being studied.7
- CDC “Flu Symptoms & Severity.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 29 Jun 2011. Available at: <http://www.cdc.gov/flu/about/disease/symptoms.htm>. Accessed May 22, 2012.
- CDC. “2011-2012 Influenza Season Week 19 ending May 12, 2012.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 18 May 2012. Available at: <http://www.cdc.gov/flu/weekly/>. Accessed May 22, 2012.
- CDC. “Types of Influenza Viruses.” Centers for Disease Control and Prevention. CDC, 22 Mar 2012. Available at: <http://www.cdc.gov/flu/about/viruses/types.htm>. Accessed May 14, 2012.
- Bush RM, et al. Positive selection on the H3 hemagglutinin gene of human influenza virus A. Mol Biol Evol. 1999 Nov;16(11):1457—65.
- CDC. “Vaccine Selection for the 2011-2012 and 2012-2013 Influenza Seasons.” Centers for Disease Control and Prevention. CDC, 23 Feb 2012. Available at: <http://www.cdc.gov/flu/about/qa/vaccine-selection.htm>. Accessed May 14, 2012.
- CDC. “Selecting the Viruses in the Seasonal Influenza (Flu) Vaccine.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 09 Mar 2011. Available at: <http://www.cdc.gov/flu/professionals/vaccination/virusqa.htm>. Accessed May 17, 2012
- World Health Organization. “Questions and Answers Recommended composition of influenza virus vaccines for use in the northern hemisphere 2012-2013 influenza season.” World Health Organization. World Health Organization, 9 Mar 2012. Available at: <http://www.who.int/influenza/vaccines/virus/recommendations/201202_qanda_recommendation.pdf>. Accessed May 6, 2012.
- USFDA Center for Biologics Evaluation and Review. “SUMMARY MINUTES VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE.” Food and Drug Administration. USFDA, 28-29 Feb 2012. Available at: <http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM296193.pdf>. Accessed May 14, 2012.
- USFDA. “Questions and Answers – FluMist Quadrivalent (Influenza Virus Vaccine Live, Intranasal).” U.S. Food and Drug Administration. USFDA, 1 Mar 2012.
Available at: <http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm294078.htm>. Accessed May 6, 2012.
- CDC “Key Facts About Seasonal Flu Vaccine.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 6 July 2012. Available at: <http://www.cdc.gov/flu/protect/keyfacts.htm>. Accessed Aug 8, 2012.
- CDC “Fluzone High-Dose Seasonal Influenza Vaccine.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 16 July 2012. Available at: <http://www.cdc.gov/flu/protect/vaccine/qa_fluzone.htm>. Accessed Aug 8, 2012.
- CDC “Who Should Get Vaccinated Against Influenza.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 9 Sept 2011. Available at: <http://www.cdc.gov/flu/protect/whoshouldvax.htm>. Accessed Aug 8, 2012.
- CDC. “Update: Influenza A (H3N2)v Transmission and Guidelines — Five States, 2011.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 06 Jan 2012. Available at: <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6051a4.htm>. Accessed May 13, 2012.
- CDC. “First H3N2 Variant Virus Infection Reported For 2012.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 12 Apr 2012. Available at: <http://www.cdc.gov/flu/spotlights/h3n2v-variant-utah.htm>. Accessed May 6, 2012.
- CDC. “Key Facts about Human Infections with Variant Viruses (Swine Origin Influenza Viruses in Humans).” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 13 Apr 2012. Available at: <http://www.cdc.gov/flu/swineflu/keyfacts-variant.htm>. Accessed May 6, 2012.