Protective memory responses are modulated by priming events prior to challenge

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Highly pathogenic H5N1 avian influenza A viruses pose a pandemic threat.
• Previous infections can influence outcomes of subsequent, virulent influenza challenges.

Purpose of the Study:

• To investigate how prior influenza A virus infections affect outcomes of secondary H5N1 avian influenza infections.
• To determine if CD8(+) T-cell responses or TNF production correlate with protection.

Main Methods:

• C57BL/6 mice were primed with either H1N1 A/Puerto Rico/8/34 (PR8) or HKx31 (H3N2) influenza viruses.
• Primed mice were subsequently challenged with a virulent H5N1 virus (A/Vietnam/1203/04, DeltaVn1203).
• Survival rates, viral replication, weight loss, CD8(+) T-cell responses, and TNF levels were assessed.

Main Results:

• PR8-primed mice showed partial protection against DeltaVn1203 challenge, while HKx31-primed mice succumbed.
• Differential survival was observed even in antibody-deficient mice.
• Protection was lost in tumor necrosis factor-deficient (TNF(-/-)) mice, despite higher early TNF in HKx31-primed mice.

Conclusions:

• The nature of the primary influenza infection significantly influences pathological outcomes following challenge with virulent H5N1.
• Protection is not solely dependent on classical CD8(+) T-cell-mediated immunity measures.
• Tumor necrosis factor (TNF) plays a critical role in mediating protection, suggesting complex immune interactions in secondary influenza infections.