Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) cause severe respiratory infections in children, the elderly, and immunocompromised adults.
• Neutralizing antibodies against the viral fusion (F) glycoprotein correlate with protection, but current responses lack cross-neutralization between hRSV and hMPV.

Purpose of the Study:

• To design and evaluate chimeric F proteins capable of eliciting cross-neutralizing antibody responses against both hRSV and hMPV.
• To provide a proof of principle for developing single immunogens against multiple human pneumoviruses.

Main Methods:

• Designed chimeric F proteins by swapping antigenic sites between hRSV F and hMPV F based on crystal structures.
• Monitored antigenic changes using ELISA with virus-specific monoclonal antibodies.
• Inoculated mice with chimeric proteins and assessed resultant antibody responses and protection against viral challenge.

Main Results:

• Chimeric F proteins successfully induced polyclonal antibody responses with cross-neutralizing activity against both hRSV and hMPV.
• Mice immunized with chimeras were protected against challenge with the virus corresponding to the grafted antigenic site.
• Demonstrated that specific antigenic site modifications can break the species-specific antibody response.

Conclusions:

• Chimeric fusion proteins represent a viable strategy for creating single immunogens that induce protective, cross-neutralizing immunity against multiple human pneumoviruses.
• This approach holds significant potential for developing novel vaccines against severe respiratory infections caused by hRSV and hMPV.