Objective:

To address comments regarding the immunogenicity of neuraminidase (NA) antibodies in older adults following vaccination with enhanced influenza vaccines, specifically focusing on the variability of NA content and the appropriateness of using a ≥ 4-fold rise in NAI antibody titers as an endpoint.

Key Findings:

• NA content is not standardized across influenza vaccine formulations, raising concerns about vaccine efficacy.
• Higher NA protein content in HD-IIV3 did not significantly increase NAI antibody titers compared to SD-IIV4, suggesting that NA content alone may not predict immunogenicity.
• Postvaccination seroconversion rates may misclassify individuals with pre-existing protective antibody levels, complicating the assessment of vaccine effectiveness.

Interpretation:

NA protein content alone does not predict immunogenicity in inducing NAI antibodies; additionally, baseline antibody levels can negatively affect postvaccination responses, indicating a need for more nuanced evaluation.

Limitations:

• Inability to quantify NA protein content in MF59-adjuvanted vaccines due to adjuvant presence limits the comprehensiveness of the findings.
• Lack of vaccine vials for further analysis post-study restricts the ability to validate results.

Conclusion:

Future research should focus on understanding the determinants of NA immunogenicity, including the role of baseline antibody levels, and establishing better-defined immunological endpoints for protection.