Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350

Abstract

Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1st or the 3rd position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3rd position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.

Expression and immunogenic characterization of recombinant gp350 for developing a subunit vaccine against Epstein-Barr virus

“…Therefore, the recombinant gp350 1-443 induced stronger lymphoproliferative responses than RVVgp150. Recombinant gp350 expressed in CHO cells (Cui et al 2013) and measles virus (Mok et al 2012) have been shown to induce significantly high-level production of IL-4 and IFN-γ. The splenocytes from gp350 1-443 -immunized mice also displayed increased production of IFN-γ, TNF-α, IL-4, and IL-10.…”

Recombinant measles virus incorporating heterologous viral membrane proteins for use as vaccines

“…The second more recent study (Mok et al, 2012) also demonstrated protection from RSV challenge using rMVs expressing RSV-F in the cotton rat model. The RSV-F molecule that was cloned was C-terminally truncated (i.e.…”

“…Recombinant measles vectors may be considered for the construction of paediatric vaccines for other paramyxoviruses such as mumps virus (Wang et al, 2001) or respiratory syncytial virus (RSV) (Mok et al, 2012;Sawada et al, 2011;Yamaji & Nakayama, 2014). The attenuated mumps virus is already included in the paediatric cocktail vaccine together with measles and rubella viruses (MMR).…”

Advances in and the potential of vaccines for respiratory syncytial virus

“…Following RSV/A2 challenge, the vaccinated cotton rats were protected from pulmonary replication. This vaccine was also evaluated in rhesus macaques, where it showed similar efficacy inducing a strong RSV F-specific antibody response [153].…”