Th1 memory differentiates recombinant from live herpes zoster vaccines

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su) offers higher protection against herpes zoster (HZ) than the live attenuated zoster vaccine (ZV).
• Understanding the immunological basis for these differing efficacies is crucial for vaccine development and public health strategies.

Purpose of the Study:

• To compare the immune responses elicited by the HZ/su and ZV vaccines in adults aged 50 to 85.
• To elucidate the immunologic mechanisms underlying the superior efficacy of the HZ/su vaccine.

Main Methods:

• Utilized FluoroSpot and flow cytometry to analyze gE-specific T cell responses before and after vaccination.
• Quantified CD4+ and CD8+ T cell responses, including IL-2 production and cytotoxic/effector functions.
• Conducted mediation analyses to assess the role of T cell responses in vaccine persistence.

Main Results:

• Both vaccines increased gE-specific T cell responses, but HZ/su induced responses at least 10-fold higher than ZV at peak memory response (PMR).
• HZ/su recipients exhibited higher gE-specific CD4+ and CD8+ T cell responses, with greater IL-2 production, while cytotoxic and effector responses were lower compared to ZV.
• At 1 year post-vaccination, Th1 and IL-2+ spot-forming cells remained significantly higher in HZ/su recipients, with IL-2+ PMR being critical for Th1 response persistence.

Conclusions:

• The HZ/su vaccine elicits a demonstrably superior and more persistent T cell memory response compared to the ZV vaccine.
• IL-2+ T cell responses are essential for maintaining Th1 responses, highlighting their importance in the long-term efficacy of herpes zoster vaccines.
• The findings underscore the immunological advantages of the HZ/su vaccine, providing a basis for its enhanced protection against shingles.