Past, present and future of RSV and PIV vaccines and anti-RSV antibodies for the protection of humans against RSV

Abstract

The human respiratory syncytial virus (RSV) is a human pathogen that infects infants, children under 2 years of age and elderly people, causing a lower respiratory tract infection, while evading the host's adaptive immune response. This review summarises the efforts to develop a safe vaccine and synthetic antibodies for immunisation of infants and children at risk. The first formalin-inactivated human RSV vaccine, FI-RSV, was developed and tested during the 1960s in infants and children. The results of this human trial revealed that control children, who were not vaccinated, recovered from RSV infection, while the vaccinated children required hospitalisation and two infants died. These results led to attempts to develop a cold-passage, temperature-sensitive (cpts) attenuated RSV vaccine. This vaccine was tested in small laboratory animals, monkeys and chimpanzees, and finally in children. The results of the human trial (published in 2005) revealed that the cpts vaccine was over-attenuated. RSV recombinants and parainfluenza virus recombinants developed in additional studies were tested in small laboratory animals. The unsuccessful attempts to produce an RSV vaccine led to the development of humanised anti-RSV mouse monoclonal antibodies (palivizumab) that were approved by the FDA for passive immunisation of infants and children at risk of aggravated RSV disease. Recent studies with formalin-inactivated bovine RSV vaccine formulated with the adjuvant monophosphoryl lipid A (MPL) protected newborn calves against RSV challenge. It is suggested that an apathogenic attenuated RSV deletion mutant, formulated with MPL and devoid of the viral genes that result in evasion of the human adaptive immune response, may be a useful vaccine.

Keywords::

• adjuvants for vaccines
• animal RSV vaccinations
• FI-RSV vaccine
• human RSV vaccine trials
• live RSV cpts
• palivizumab
• passive immunisation
• pathogenic RSV mutant
• RSV PFP vaccine
• xenogeneic PIV vaccines

Acknowledgements

The author thanks G Fuchs, Yissum Technology Transfer Company of the Hebrew University of Jerusalem, for his help with the RSV patents, and C Balshayi for her help with the manuscript.