Establishing Immune Correlates of Protection Against Respiratory Syncytial Virus Infection to Accelerate Vaccine...

Area of Science:

• Immunology
• Vaccinology
• Epidemiology

Background:

• Respiratory syncytial virus (RSV) poses a significant health burden, particularly in older adults.
• Developing effective RSV vaccines is crucial for public health.
• Identifying reliable immunogenicity markers can accelerate vaccine development and evaluation.

Purpose of the Study:

• To quantify the relationship between vaccine-induced immunogenicity and protection against RSV clinical outcomes.
• To evaluate immunogenicity as a surrogate marker for vaccine efficacy (VE) in RSV vaccine development.
• To explore the role of serum neutralizing activity (SNA) and cell-mediated immunity (CMI) as immunogenicity endpoints.

Main Methods:

• Two meta-analytical approaches were applied to data from seven randomized placebo-controlled trials of RSV vaccines in older adults.
• Examined the correlation between SNA and VE across three clinical severity levels: acute respiratory infection, RSV lower respiratory tract disease (LRTD) with ≥2 symptoms, and LRTD with ≥3 symptoms (LRTD 3+).
• Explored the additional contribution of CMI to VE, adjusting for SNA.

Main Results:

• A positive correlation was observed between SNA and VE across all three clinical severity levels.
• Higher CMI was associated with increased VE, particularly for the most severe clinical outcome (RSV LRTD 3+).
• These findings suggest CMI may offer additional clinical benefits in reducing RSV infection severity.

Conclusions:

• Preliminary evidence supports immune correlates of protection against RSV infection.
• SNA and CMI show potential as surrogate markers for vaccine efficacy in RSV vaccine trials.
• These findings may accelerate the development of novel RSV vaccines.