Influenza Vaccines

Introduction to Influenza Vaccines

Influenza vaccines are crucial public health tools designed to prevent and mitigate the impact of seasonal and pandemic influenza. These vaccines have been in use for decades and continue to evolve to meet the challenges posed by the ever-changing influenza viruses.

Key points:

  • First influenza vaccine developed in the 1940s
  • Annual reformulation to match circulating strains
  • Essential component of global influenza prevention strategies
  • Recommended for widespread use, especially in high-risk populations
  • Ongoing research focuses on developing universal influenza vaccines

Influenza Virus and Disease

Influenza Viruses

  • RNA viruses of the Orthomyxoviridae family
  • Four types: A, B, C, and D (A and B cause seasonal epidemics)
  • Subtypes of Influenza A based on surface proteins (hemagglutinin and neuraminidase)
  • Undergo frequent antigenic drift and occasional antigenic shift

Influenza Disease

  • Acute respiratory illness characterized by fever, cough, myalgia, and fatigue
  • Incubation period: 1-4 days
  • Can lead to severe complications, especially in high-risk groups
  • Annual global burden: 3-5 million severe cases and 290,000-650,000 deaths

Transmission

Primarily spread through respiratory droplets and contact with contaminated surfaces. Highly contagious, especially in closed settings.

Types of Influenza Vaccines

Several types of influenza vaccines are currently available:

1. Inactivated Influenza Vaccines (IIV)

  • Most common type
  • Contain inactivated virus particles
  • Administered intramuscularly
  • Subtypes: Trivalent (IIV3) and Quadrivalent (IIV4)

2. Live Attenuated Influenza Vaccine (LAIV)

  • Contains weakened live viruses
  • Administered intranasally
  • Quadrivalent formulation
  • Approved for use in certain age groups

3. Recombinant Influenza Vaccine (RIV)

  • Produced using recombinant DNA technology
  • Does not require egg-based production
  • Quadrivalent formulation (RIV4)

4. Cell-Culture-Based Vaccines

  • Produced using cell culture rather than eggs
  • Potential for faster production
  • Quadrivalent formulation

5. Adjuvanted Vaccines

  • Contain an adjuvant to enhance immune response
  • Particularly useful in older adults
  • Example: MF59-adjuvanted vaccine

Influenza Vaccine Development

Strain Selection Process

  • WHO Global Influenza Surveillance and Response System (GISRS) monitors circulating strains
  • Biannual WHO consultations for strain recommendations (February for Northern Hemisphere, September for Southern Hemisphere)
  • Strains selected based on antigenic and genetic analyses, epidemiological data, and vaccine efficacy studies

Production Methods

  • Egg-based production: Traditional method, takes about 6 months
  • Cell-based production: Faster, not dependent on egg supply
  • Recombinant technology: Rapid production, highly scalable

Composition

Typically includes:

  • Two Influenza A strains (H1N1 and H3N2)
  • One or two Influenza B strains (Victoria and/or Yamagata lineages)

Efficacy and Safety of Influenza Vaccines

Efficacy

  • Varies annually depending on match between vaccine and circulating strains
  • Typical efficacy: 40-60% when well-matched
  • Can reduce severity of illness even when not fully protective
  • Effectiveness may be lower in certain populations (e.g., older adults)

Safety Profile

  • Generally well-tolerated
  • Common side effects: Injection site reactions, mild systemic symptoms
  • Rare adverse events: Guillain-Barré syndrome (1-2 cases per million vaccinations)
  • LAIV: Contraindicated in certain groups due to theoretical risks

Duration of Protection

Protection typically lasts through one influenza season but can wane over time, especially in older adults. Annual vaccination is recommended due to antigenic drift and waning immunity.

Influenza Vaccination Schedule

Timing

  • Annual vaccination recommended
  • Optimal timing: Early fall, before influenza activity begins
  • Can be given throughout influenza season

Dosing

  • Adults and children ≥9 years: Single dose annually
  • Children 6 months to 8 years:
    • Two doses (separated by at least 4 weeks) if first time receiving influenza vaccine or if vaccination history is unknown
    • Single dose if previously received ≥2 doses of influenza vaccine

Route of Administration

  • IIV and RIV: Intramuscular injection
  • LAIV: Intranasal spray

Influenza Vaccination in Special Populations

Pregnant Women

  • Recommended at any stage of pregnancy
  • IIV preferred; LAIV contraindicated
  • Provides protection to both mother and infant

Older Adults (≥65 years)

  • High-dose or adjuvanted vaccines may be preferable
  • Important due to increased risk of complications

Immunocompromised Individuals

  • IIV or RIV recommended; LAIV contraindicated
  • May have reduced vaccine response

Healthcare Workers

  • Annual vaccination strongly recommended
  • Important for protecting both workers and patients

Children

  • Recommended for all children ≥6 months
  • LAIV an option for healthy children ≥2 years in some countries

Challenges and Considerations in Influenza Vaccination

Antigenic Drift and Shift

  • Constant viral evolution necessitates annual vaccine updates
  • Potential for pandemic strains through antigenic shift

Vaccine Hesitancy

  • Misconceptions about vaccine safety and efficacy
  • Need for effective public health communication

Production Challenges

  • Time constraints in egg-based production
  • Potential for mutations during egg adaptation

Variable Effectiveness

  • Efficacy depends on match with circulating strains
  • Reduced effectiveness in certain populations

Global Access and Equity

  • Disparities in vaccine availability and distribution
  • Need for improved global vaccination strategies

Future Directions in Influenza Vaccination

Universal Influenza Vaccine

  • Targeting conserved viral proteins
  • Potential for broader, longer-lasting protection
  • Multiple candidates in clinical trials

Improved Production Methods

  • Advancing cell-based and recombinant technologies
  • Exploring mRNA vaccine platforms

Enhanced Delivery Systems

  • Microneedle patches for painless administration
  • Oral and sublingual vaccine formulations

Personalized Vaccination Approaches

  • Tailoring vaccines based on individual immune responses
  • Optimizing vaccination strategies for specific populations

Improved Surveillance and Prediction

  • Enhancing global surveillance networks
  • Utilizing big data and AI for strain prediction


Influenza Vaccines
  1. Q: What types of influenza viruses do seasonal flu vaccines typically protect against? A: Influenza A (H1N1 and H3N2) and Influenza B
  2. Q: How often are influenza vaccine compositions updated? A: Annually
  3. Q: What is the most common method of administering influenza vaccines? A: Intramuscular injection
  4. Q: What is the minimum age for receiving most influenza vaccines? A: 6 months
  5. Q: How many doses of influenza vaccine are recommended for children 6 months to 8 years receiving it for the first time? A: 2 doses
  6. Q: What is the interval between doses for children requiring two doses of influenza vaccine? A: At least 4 weeks
  7. Q: What is the name of the intranasal influenza vaccine? A: FluMist (LAIV)
  8. Q: What type of influenza vaccine is FluMist? A: Live attenuated influenza vaccine (LAIV)
  9. Q: What is the age range for which FluMist is approved in the US? A: 2-49 years old
  10. Q: What is the typical effectiveness of seasonal influenza vaccines? A: 40-60%
  11. Q: In which month does influenza vaccination typically begin in the Northern Hemisphere? A: September or October
  12. Q: What is the name of the high-dose influenza vaccine designed for older adults? A: Fluzone High-Dose
  13. Q: How many influenza virus strains does a quadrivalent vaccine contain? A: 4 strains
  14. Q: What is the main advantage of cell-based influenza vaccines over egg-based vaccines? A: Faster production and avoidance of egg-adapted changes
  15. Q: What is the name of the first approved recombinant influenza vaccine? A: FluBlok
  16. Q: What protein is produced using recombinant DNA technology in FluBlok? A: Hemagglutinin (HA)
  17. Q: What is the typical dosage of standard-dose influenza vaccines for individuals 3 years and older? A: 0.5 mL
  18. Q: What is the reduced dosage of some influenza vaccines for children 6-35 months old? A: 0.25 mL
  19. Q: What is the storage temperature requirement for most influenza vaccines? A: 2-8°C (35-46°F)
  20. Q: How long does it typically take for immunity to develop after influenza vaccination? A: About 2 weeks
  21. Q: What is the name of the adjuvanted influenza vaccine designed for older adults? A: Fluad
  22. Q: What is the adjuvant used in Fluad? A: MF59
  23. Q: In which year was the first influenza vaccine licensed for use in the United States? A: 1945
  24. Q: What percentage of the global population is estimated to be affected by seasonal influenza annually? A: 5-10%
  25. Q: What is the estimated number of deaths caused by seasonal influenza globally each year? A: 290,000 to 650,000
  26. Q: What is the main surface glycoprotein targeted by most influenza vaccines? A: Hemagglutinin (HA)
  27. Q: What is antigenic drift in the context of influenza viruses? A: Small, gradual changes in the virus genes
  28. Q: What is antigenic shift in the context of influenza viruses? A: Abrupt, major change in influenza A viruses
  29. Q: Which influenza virus type is capable of causing pandemics? A: Influenza A
  30. Q: What is the name of the global surveillance network that monitors influenza virus evolution? A: Global Influenza Surveillance and Response System (GISRS)


Further Reading
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