Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus...

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Measles poses a significant global health challenge, exacerbated by vaccination difficulties in young infants.
• Developing safe and effective measles vaccines that provide long-lasting protective immunity is crucial.

Purpose of the Study:

• To develop and evaluate novel Sindbis virus replicon particles (SIN-H and SIN-F) for measles vaccination.
• To assess the safety, immunogenicity, and protective efficacy of these novel vaccine candidates.

Main Methods:

• Sindbis virus replicon particles expressing measles virus (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins were developed.
• Immunogenicity was assessed in mice and non-human primates (macaques) by measuring MV-neutralizing antibodies and T cell responses (IFN-gamma).
• Protective efficacy was evaluated by challenging vaccinated macaques with wild-type MV.

Main Results:

• A single dose of SIN-H induced high-titered, dose-dependent MV-neutralizing antibodies in mice.
• Vaccination of macaques with SIN-H resulted in sustained MV-neutralizing antibody and IFN-gamma-producing memory T cells.
• Most vaccinated macaques were protected from rash upon wild-type MV challenge 18 months post-vaccination, with biphasic T cell responses observed after challenge.

Conclusions:

• Sindbis virus replicon particles expressing MV proteins are a viable strategy for inducing sustained protective immunity against measles.
• The study highlights the prolonged and complex nature of measles virus clearance post-infection, influenced by prior vaccination.