Immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys

Abstract

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants. Effective vaccines are currently being sought, but no vaccine is thus far available. In our previous study, recombinant AIK-C measles vaccine expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective immunity against RSV demonstrated in cotton rats. In the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were detected and no infectious virus was recovered from the lungs of monkeys immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to inhibit RSV infection.

Measles-vectored vaccine approaches against viral infections: a focus on Chikungunya

“…Development of a vaccine against RSV has been identified as a priority by WHO based on the large global burden, particularly in neonates and young infants [1,2]. Various MVbased RSV candidates have been developed and have been shown to protect NHP or cotton rats against challenge [34,35,[99][100][101]. Concerning viral hepatitis, the global burden is still increasing and is predominantly caused by Hepatitis B and C [1], emphasizing the need for additional measures.…”

Versatility of live-attenuated measles viruses as platform technology for recombinant vaccines

“…Interestingly, the diversity of the MeV strains used as backbones for the vaccine candidates against pathogens transmitted via the respiratory route was highest among all disease subgroups. Edmonston B 32 , 48 – 50 or its derivatives Edmonston Zagreb 39 , 41 , 43 , Moraten 33 , 38 , 42 , Schwarz 31 , 34 – 36 (that shares 100% nucleotide identity with Moraten), or the temperature-sensitive AIK-C 40 , 44 , 45 , 51 – 53 vaccine strains were successfully tested. Moreover, even the wild-type HL strain 48 or an attenuated clone of HL 49 , which was generated by genetically interfering with expression of the MeV accessory protein and virulence factor V 54 , were used to generate potential vaccines.…”

“…Syrian hamsters turned out to be a good rodent model for COVID-19 pathogenesis and were predominantly used to analyze immune responses and protection of experimental vaccines against SARS-CoV-2 32 , 34 , 38 , having also been used successfully to demonstrate efficacy of the MeV-derived NiV vaccine 48 . Non-human primates are the only natural hosts of MeV other than humans and are not used as frequently as rodents, but vaccination of African green monkeys 48 , cynomolgus macaques 46 , 47 , 49 , 53 , and rhesus macaques 41 have shown immunogenicity or efficacy for the MeV-vaccines against NiV 48 , IAV 49 , LASV 46 , 47 , or RSV 41 , 53 .…”

“…In these different animal models, binding antibodies were detected by ELISA after vaccination. For six out of nine target viruses, target-specific nAbs were induced, namely for RSV 39 – 41 , 45 , 51 , 53 , LASV 46 , MERS-CoV 33 , 42 , SARS-CoV 31 , 43 , or SARS-CoV-2 32 , 34 – 36 , 38 . These reached maximum neutralizing titers of up to 4000 PRNT 50 for SARS-CoV-2 34 , 1000 IC 50 for SARS-CoV 31 , and a VNT of 874 for MERS-CoV 33 .…”

“…Encouraged by these results, this vaccine candidate has been transferred into a clinical Phase I study (NCT04055454). For vaccines against IAV 52 or RSV 39 – 41 , 45 , 51 in cotton rats, highly pathogenic avian IAV 49 or RSV 53 in cynomolgus macaques, MERS-CoV 33 or SARS-CoV 31 in IFNAR −/− -CD46Ge mice, or SARS-CoV-2 in IFNAR −/− mice 32 , 34 , IFNAR −/− -CD46Ge mice 38 , or in Syrian hamsters 32 , 34 , 38 , protection was demonstrated by reduced or undetectable histopathological changes, and the absence (or low levels) of infectious virus, viral proteins, or viral RNA in vaccinated animals. Regarding protection against SARS-CoV, the height of nAb titers correlated with the degree of protection during challenge 31 .…”