Perspectives on pandemics: a research agenda

Area of Science:

• Virology
• Epidemiology
• Immunology

Background:

• The 20th century witnessed major influenza pandemics in 1918, 1957, and 1968.
• Pandemics of 1957 (A/H2N2) and 1968 (A/H3N2) involved substantial antigenic alterations, likely due to animal virus gene reassortment.
• The 1918 pandemic, though not directly studied virologically, is inferred from seroarcheology to be similar to current swine influenza A virus (H1N1).

Purpose of the Study:

• To analyze the historical antigenic changes in human influenza viruses throughout the 20th century.
• To investigate the potential role of specific influenza virus subtypes (H1N1, H2N2, H3N2) in pandemic emergence.
• To assess the implications of viral evolution for vaccine efficacy and pandemic preparedness.

Main Methods:

• Review of historical influenza pandemic data from the 20th century.
• Analysis of seroarcheological evidence for the 1918 influenza pandemic.
• Examination of antigenic changes in human influenza A virus subtypes (H1N1, H2N2, H3N2) over time.

Main Results:

• Antigenic shifts in A/H2N2 and A/H3N2 viruses were linked to pandemics in 1957 and 1968.
• A/H1N1 subtype viruses may represent a 'default' human influenza strain, evidenced by multiple periods of prevalence.
• Antigenic changes in A/H1N1 in 1947 led to vaccine failure and subsequent pandemic spread.

Conclusions:

• Historical influenza pandemics are characterized by significant viral antigenic evolution, often involving reassortment with animal viruses.
• The A/H1N1 subtype has shown a propensity for pandemic emergence, though the long-term dominance of A/H3N2 presents a complex picture.
• While only H1, H2, H3, N1, and N2 antigens have been identified in human influenza, the possibility of novel antigens contributing to future pandemics cannot be excluded based on the limited virologic history.