Influenza Virus and Vaccines Study Guide

Vaccines Lecture Notes

Lecture Overview

  • Institution: University of Kent

  • Instructor: Dr. Emma Hargreaves

  • Course: BIOS6150

  • Topic: Influenza Virus and Vaccines

Transcript Breakdown

1. Introduction to Influenza Virus
  • Type: Negative sense RNA genome

  • Classification: Family Orthomyxoviridae

  • Genera & Species:     - Alphainfluenzavirus (Influenza A virus)     - Betainfluenzavirus (Influenza B virus)     - Gammainfluenzavirus (Influenza C virus)     - Deltainfluenzavirus (Influenza D virus)   - Note: Distinct strains affect mammals but some variants infect fish and amphibians.

2. Subtypes and Lineages of Influenza Virus
  • Influenza A Virus:   - Total subtypes based on surface antigens: 18 HA (H1–H18), 11 NA (N1–N11)   - Currently circulating in humans: A(H1N1)pdm09 (pandemic strain), A(H3N2)   - Key Point: Only Influenza A causes pandemics.

  • Influenza B Virus:   - Classification based on lineages: B/Yamagata and B/Victoria   - Higher morbidity and mortality in children, constituting about 23% of global cases.

  • Influenza C Virus: Less frequently detected, causes milder diseases.

  • Influenza D Virus: Primarily affects cattle; no known infections in humans.

3. Influenza Burden and Eradication Possibility
  • Annual Impact: Influenza B associated with an estimate of 23% of influenza cases globally.   - Contributes approximately 7.9 million lower respiratory infections and 1.4 million hospital admissions each year.   - Highest burden seen in school-aged children (0-18 years), with 52% of pediatric deaths attributed to Influenza B.

  • Economic Cost: US$3.5 billion annually in healthcare surcharges; 37% attributed to Influenza B.

  • Eradication Viability:   - No animal reservoir for the Influenza B virus, making eradication conceivably easier than Influenza A.   - Lack of evidence for significant animal reservoirs creates a pathway for potential eradication strategies.

4. Mechanisms of Influenza Transmission
  • Transmission Routes:   - Droplets: >10 μm; primarily affect upper respiratory tract.   - Aerosols: <5 μm; reach lower respiratory tract.   - Direct Contact: Transmitted via mucus membranes through both direct interaction and contaminated objects.

  • Contributing Factors:   - Environmental conditions (humidity, temperature), vaccination status, age, social interactions affect viral transmission.

5. Influenza Symptoms
  • Typical symptoms include:   - Sudden onset of fever   - Dry cough (may persist >2 weeks)   - Headaches   - Muscle/joint pain   - Severe malaise   - Sore throat   - Runny nose

  • Most individuals recover within a week, but severity varies.

6. Population at Higher Risk
  • Age Risk Groups:   - Adults aged 65+   - Children under 2 years   - Pregnant individuals

  • Associated Health Issues:   - Chronic lung diseases, heart diseases, blood disorders such as sickle cell disease, metabolic disorders, immune system disorders, neurological conditions.

7. Influenza Pathophysiology
  • Direct Pathology: Viral replication leads to lung inflammation and epithelial cell death (both apoptosis and necrosis).

  • Immune Response: Both innate (cytokine production, immune cell recruitment) and adaptive responses causing exacerbated inflammation and potential tissue damage.

  • Key Complications: Acute pneumonia in 30-40% of hospitalized cases, predominantly from Influenza A.

8. Antigenic Drift and Shift
  • Antigenic Drift: Gradual mutations in the virus leading to variability.

  • Antigenic Shift: Reassortment of genome segments leading to new strain formation, which may cause pandemics.

9. Influenza Therapeutics
  • Existing Treatments:   - Neuraminidase inhibitors (NAIs): Oseltamivir, Zanamivir   - M2 ion channel inhibitors: Amantadine, Rimantadine

  • Research: Ongoing studies target drug resistance and bioavailability improvements.

10. Challenges in Influenza Vaccine Development
  • Complexity due to rapid mutations and variability among strains.   - H and N proteins involved in cell entry and infection: 18 H types and 11 N types.

  • Vaccine Development Timeline: Vaccines produced approximately 6 months prior to flu season; effectiveness varies annually (historically around 52% - 70%).

11. Vaccination Strategies in the UK
  • Current vaccines used based on age groups and clinical risk:   - For ages 6 months to <2 years: IIVC or LAIV   - Ages 2-18 in clinical risk: IIVC or LAIV   - Adults 18-64 in clinical risk: IIVC or IIVr   - Ages 65 and older: IIV-HD or adjuvanted vaccines.

12. Conclusion and Future Directions
  • Vaccines under development targeting multiple strains simultaneously (multivalent nucleoside-modified mRNA vaccines) may provide broader protection.

  • Importance of continued research and public health measures to improve vaccine effectiveness and reduce flu burden annually.