Influenza, commonly known as the flu, is a contagious respiratory illness caused by influenza viruses. Annual vaccination is the primary method for preventing influenza and its complications. However, the effectiveness of influenza vaccines can vary each year due to the virus’s ability to mutate and the challenge of predicting which strains will be most prevalent. This essay explores the effectiveness of influenza vaccines, the process of their development, and the factors that influence their efficacy.

Effectiveness of Influenza Vaccines

The effectiveness of influenza vaccines can be measured by their ability to prevent influenza infection, reduce the severity of illness, and decrease the risk of complications. Several factors influence vaccine effectiveness, including the match between the vaccine strains and circulating strains, the age and health status of the individual, and the type of vaccine administered.

  1. Match Between Vaccine Strains and Circulating Strains
    • The effectiveness of influenza vaccines largely depends on how well the strains included in the vaccine match the strains that are circulating in the community. Each year, the World Health Organization (WHO) and other health authorities make predictions about which strains are most likely to circulate based on global surveillance data. If the vaccine strains closely match the circulating strains, the vaccine is more likely to be effective. Conversely, if there is a significant mismatch, vaccine effectiveness can be reduced.
    • Despite efforts to accurately predict circulating strains, antigenic drift—small, gradual changes in the virus’s surface proteins—can lead to the emergence of new strains that differ from those included in the vaccine. This antigenic drift is one reason why influenza vaccines need to be updated annually.
  2. Age and Health Status of the Individual
    • The effectiveness of influenza vaccines can vary based on the age and health status of the individual receiving the vaccine. Generally, vaccines tend to be more effective in healthy adults and children. In older adults, immune responses to the vaccine can be weaker due to age-related declines in the immune system, leading to lower vaccine effectiveness. However, even when the vaccine is less effective in preventing infection in older adults, it can still reduce the severity of illness and the risk of complications, such as hospitalization and death.
    • Individuals with certain chronic health conditions, such as asthma, diabetes, or heart disease, may also have a reduced immune response to the vaccine. However, vaccination remains important for these individuals because it can still provide protection against severe illness and complications.
  3. Type of Vaccine Administered
    • Several types of influenza vaccines are available, including inactivated influenza vaccines (IIV), live attenuated influenza vaccines (LAIV), and recombinant influenza vaccines (RIV). Each type has different properties and may be more or less effective in different populations.
    • Inactivated Influenza Vaccine (IIV): This vaccine contains killed virus particles and is administered via injection. It is suitable for most individuals, including those with weakened immune systems. IIV is available in both trivalent (three strains) and quadrivalent (four strains) formulations.
    • Live Attenuated Influenza Vaccine (LAIV): This vaccine contains live, weakened virus particles and is administered via nasal spray. It is recommended for healthy individuals aged 2-49 years who are not pregnant. LAIV is also available in trivalent and quadrivalent formulations.
    • Recombinant Influenza Vaccine (RIV): This vaccine is produced using recombinant DNA technology and does not require the use of eggs or live virus. It is administered via injection and is available as a quadrivalent vaccine. RIV is suitable for individuals with egg allergies and may offer advantages in terms of production speed and scalability.

Development of Influenza Vaccines

The development of influenza vaccines is a complex, multi-step process that involves global surveillance, strain selection, vaccine production, and quality control. This process must be completed each year to ensure that vaccines are updated to match circulating strains.

  1. Global Surveillance
    • The first step in the development of influenza vaccines is global surveillance of influenza viruses. This surveillance is conducted by the Global Influenza Surveillance and Response System (GISRS), coordinated by the WHO. GISRS consists of a network of national influenza centers and WHO collaborating centers that collect and analyze influenza virus samples from around the world.
    • Surveillance data include information on circulating strains, their genetic and antigenic characteristics, and patterns of influenza activity. This data is critical for identifying emerging strains and making informed decisions about which strains to include in the vaccine.
  2. Strain Selection
    • Based on the surveillance data, the WHO convenes biannual meetings of the Global Influenza Vaccine Expert Group to select the strains for the upcoming influenza season. These meetings are held in February for the Northern Hemisphere and in September for the Southern Hemisphere.
    • The selected strains typically include three or four viruses: two influenza A subtypes (H1N1 and H3N2) and one or two influenza B lineages (Victoria and Yamagata). The chosen strains are intended to match the strains that are most likely to circulate in the upcoming season.
    • The WHO’s recommendations are then used by national regulatory agencies and vaccine manufacturers to produce the influenza vaccines.
  3. Vaccine Production
    • Once the strains are selected, vaccine production begins. The production process involves several steps, including virus propagation, antigen extraction, formulation, and filling.
    • Virus Propagation: The selected influenza strains are grown in fertilized chicken eggs or cell culture systems. For egg-based vaccines, the virus is injected into the eggs, where it replicates. After several days, the virus-containing fluid is harvested from the eggs. Cell-based vaccines use mammalian cell lines to grow the virus, providing an alternative to egg-based production.
    • Antigen Extraction: The harvested virus is inactivated (killed) or attenuated (weakened) for use in the vaccine. The hemagglutinin (HA) and neuraminidase (NA) antigens, which stimulate the immune response, are extracted and purified.
    • Formulation: The purified antigens are formulated into the final vaccine product. Trivalent vaccines contain antigens from three strains, while quadrivalent vaccines contain antigens from four strains. Adjuvants, which enhance the immune response, may be added to some vaccines.
    • Filling and Packaging: The formulated vaccine is filled into vials or syringes, labeled, and packaged for distribution. Rigorous quality control measures ensure that the vaccine meets safety and efficacy standards.
  4. Quality Control and Regulation
    • Throughout the production process, stringent quality control measures are implemented to ensure the safety, potency, and purity of the vaccine. This includes testing for sterility, stability, and antigen content.
    • Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), review the data and approve the vaccines for use. Once approved, the vaccines are distributed to healthcare providers and vaccination sites.

Factors Influencing Vaccine Efficacy

Several factors can influence the efficacy of influenza vaccines, including antigenic drift, antigenic shift, and individual immune responses.

  1. Antigenic Drift
    • Antigenic drift refers to the gradual accumulation of genetic mutations in the influenza virus’s HA and NA proteins. These mutations can alter the virus’s surface antigens, reducing the effectiveness of pre-existing immunity from previous infections or vaccinations.
    • Because antigenic drift occurs continuously, the influenza vaccine must be updated annually to include the most current strains. If the vaccine strains do not closely match the circulating strains due to antigenic drift, vaccine efficacy can be reduced.
  2. Antigenic Shift
    • Antigenic shift is a more abrupt and significant change in the influenza virus, resulting from the reassortment of genetic material between different influenza strains. This can lead to the emergence of a novel influenza A virus subtype with pandemic potential.
    • Antigenic shift occurs less frequently than antigenic drift but can have a profound impact on public health. The emergence of novel subtypes, such as the H1N1 pandemic strain in 2009, can lead to widespread outbreaks and increased morbidity and mortality. Current seasonal influenza vaccines may not provide protection against newly emerged subtypes, necessitating the development of new vaccines.
  3. Individual Immune Responses
    • The immune response to influenza vaccination can vary among individuals based on factors such as age, health status, and prior exposure to influenza viruses. Younger individuals and those with robust immune systems tend to mount stronger immune responses to the vaccine.
    • In older adults and individuals with weakened immune systems, the immune response to the vaccine may be less robust, resulting in lower vaccine efficacy. Strategies such as high-dose vaccines or adjuvanted vaccines can enhance the immune response in these populations.

Improving Influenza Vaccine Effectiveness

Ongoing research and development efforts aim to improve the effectiveness of influenza vaccines through new technologies, better strain selection, and enhanced formulations.

  1. Universal Influenza Vaccines
    • One of the most promising areas of research is the development of universal influenza vaccines that provide broad and long-lasting protection against multiple influenza strains. Universal vaccines target conserved regions of the influenza virus, such as the stem of the HA protein, which undergoes less frequent mutation.
    • By eliciting a broader immune response, universal vaccines have the potential to provide protection against both seasonal and pandemic influenza strains, reducing the need for annual updates.
  2. Advancements in Vaccine Production
    • Advances in vaccine production technologies, such as recombinant DNA technology and cell-based manufacturing, can improve the speed and scalability of vaccine production. These technologies also eliminate the need for eggs, reducing the risk of egg-related allergies and increasing production flexibility.
    • mRNA vaccines, which have shown remarkable efficacy against COVID-19, are being explored for influenza vaccination. mRNA vaccines can be rapidly developed and produced, offering the potential for quicker responses to emerging influenza strains.
  3. Enhanced Vaccine Formulations
    • Developing enhanced vaccine formulations, such as high-dose vaccines and adjuvanted vaccines, can improve immune responses in populations with lower vaccine efficacy, such as older adults. Adjuvants enhance the immune response by stimulating the immune system, leading to stronger and longer-lasting protection.
    • Intranasal vaccines, such as LAIV, offer an alternative to injectable vaccines and can stimulate mucosal immunity in the respiratory tract, providing an additional layer of protection against influenza infection.
  4. Improved Strain Selection and Surveillance
    • Enhancing global surveillance and strain selection processes can improve the accuracy of predictions for circulating influenza strains. Advanced data analytics, genetic sequencing, and real-time monitoring can provide more comprehensive and timely information for strain selection.
    • Collaborative efforts among international health organizations, national health agencies, and vaccine manufacturers can ensure that the most current and relevant data is used for vaccine development.


Influenza vaccines are a critical tool for preventing influenza and its complications, but their effectiveness can vary each year due to the virus’s ability to mutate and the challenges of predicting circulating strains. The development of influenza vaccines involves a complex, multi-step process that includes global surveillance, strain selection, vaccine production, and quality control. Factors influencing vaccine efficacy include the match between vaccine strains and circulating strains, individual immune responses, and the occurrence of antigenic drift and shift.

Ongoing research and development efforts aim to improve the effectiveness of influenza vaccines through new technologies, better strain selection, and enhanced formulations. Universal influenza vaccines, advancements in vaccine production, enhanced vaccine formulations, and improved surveillance can contribute to more effective influenza prevention and control.

By understanding the factors that influence vaccine effectiveness and investing in innovative approaches to vaccine development, we can enhance our ability to protect populations from influenza and reduce the burden of this contagious respiratory illness.

Last Update: June 8, 2024