Influenza Vaccine Immunity
Influenza A and B are the two types of influenza viruses that cause epidemic human disease. Influenza A and B viruses are further separated into subtypes and lineages, respectively. Influenza A viruses are categorized into subtypes on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Influenza A subtypes H1N1 and H3N2 viruses co-circulate globally.
New influenza virus variants emerge as a result of point mutations and genetic recombination that occur during viral replication. Frequent emergence of antigenic variants is the reason for seasonal epidemics. Minor changes in hemagglutinin and neuraminidase are referred to as antigenic drift, and major changes are called antigenic shifts. Antigenic drifts are associated with localized outbreaks, while antigenic shifts are associated with epidemics and pandemics of influenza A.
Antigenic drift is due to a point mutation in HA and/or NA. Inefficient proofreading by influenza viral RNA polymerase results in a high incidence of transcription errors and amino acid substitutions in hemagglutinin or neuraminidase, allowing new variants to evade preexisting humoral immunity and cause influenza outbreaks. An individual immune to the original strain is not immune to the drifted one.
Antigenic shift is due to HA or NA gene reassortment that results in synthesis of new H and/or N protein variants. Wild aquatic birds are the natural hosts for all subtypes of influenza A virus. Pigs also play an important role in the evolution of human pandemic strains because pig trachea contains receptors for both avian and human influenza viruses and pigs support the growth of both types of viruses. Genetic reassortment between avian and human virus may occur in pigs, leading to a novel strain.
Influenza B viruses are separated into two distinct genetic lineages (Yamagata and Victoria) but are not categorized into subtypes. Influenza B viruses undergo antigenic drift less rapidly than influenza A viruses. Influenza B viruses from both lineages have co-circulated in most influenza seasons since the 1980s (16,17).
The composition of influenza vaccines is changed in most seasons, with one or more vaccine strains replaced annually to provide protection against viruses that are anticipated to circulate. The flu vaccine for 2016–17 contains a different influenza A(H3N2) virus and a different influenza B virus lineage from the previous year.
The 2016–17 U.S. influenza vaccines will contain HA derived from the following:
- A/California/7/2009 (H1N1)–like virus,
- A/Hong Kong/ 4801/2014 (H3N2)–like virus, and
- B/Brisbane/60/2008–like virus (Victoria lineage).
The trivalent influenza vaccines available in recent seasons have contained one influenza B virus, representing only one lineage. The proportion of circulating influenza B viruses that are of the lineage represented in the vaccine has varied. During the 11 influenza seasons from 2004–05 through 2015–16, the more prevalent circulating B lineage was represented in the vaccine in eight seasons. The 2016–17 U.S. quadrivalent vaccines will contain the same three antigens, and an additional influenza B virus HA, derived from a B/Phuket/3073/2013–like virus (Yamagata lineage).
Immune responses elicited by influenza vaccines are generally strain-specific. Antibody against one influenza virus type or subtype confers limited or no protection against another type or subtype. It usually does not confer protection against antigenic variants of the same virus that arise by antigenic drift. However, adults who have been vaccinated annually may experience a boost of antibody titers against influenza A(H3N2) viruses that have been encountered previously either by vaccination or natural infection.
Protection against viruses that are antigenically similar to those contained in the vaccine extends at least for 6 to 8 months, particularly in nonelderly populations. Because of its transient effectiveness, it is important to time vaccination with the expected onset of influenza season in your geographical location.
