Sendai virus-based RSV vaccine protects African green monkeys from RSV infection

Abstract

Respiratory syncytial virus (RSV) is a serious disease of children, responsible for an estimated 160,000 deaths per year worldwide. Despite the ongoing need for global prevention of RSV and decades of research, there remains no licensed vaccine. Sendai virus (SeV) is a mouse parainfluenza virus-type 1 which has been previously shown to confer protection against its human cousin, human parainfluenza virus-type 1 in African green monkeys (AGM). Here is described the study of a RSV vaccine (SeVRSV), produced by reverse genetics technology using SeV as a backbone to carry the full-length gene for RSV F. To test for immunogenicity, efficacy and safety, the vaccine was administered to AGM by intratracheal (i.t.) and intranasal (i.n.) routes. Control animals received the empty SeV vector or PBS. There were no booster immunizations. SeV and SeVRSV were cleared from the URT and LRT of vaccinated animals by day 10. Antibodies with specificities toward SeV and RSV were detected in SeVRSV primed animals as early as day ten after immunizations in both sera and nasal wash samples. One month after immunization all test and control AGM received an i.n. challenge with RSV-A2. SeVRSV-vaccinated animals exhibited reduced RSV in the URT compared to controls, and complete protection against RSV in the LRT. There were no clinically relevant adverse events associated with vaccination either before or after challenge. These data encourage advanced testing of the SeVRSV vaccine candidate in clinical trials for protection against RSV.

Influence of Antigen Insertion Site and Vector Dose on Immunogenicity and Protective Capacity in Sendai Virus-Based Human Parainfluenza Virus Type 3 Vaccines

“…Just as SeV is a promising Jennerian vaccine candidate against HPIV1, rSeV too is being developed as a vaccine vector against HPIV3, as reported here and in our earlier study (15), and other respiratory paramyxoviruses such as HRSV (13,14,41) and HPIV2 (16). Intranasal vaccination with the SeV-vectored HRSV vaccine, in which the HRSV F gene was inserted into the F-HN gene junction of rSeV, elicits protective immunity without causing pathology in both cotton rats (14) and African green monkeys (42). Analogous experimental trials in African green monkeys with the HPIV3 vaccine candidates described in our study are needed to compare rSeV-HPIV3HN(P-M) and rSeV-HPIV3HN(F-HN) for immunogenicity, protective capacity, and potential pathology in an animal model more closely related to humans.…”

Relationships among Dissemination of Primary Parainfluenza Virus Infection in the Respiratory Tract, Mucosal and Peripheral Immune Responses, and Protection from Reinfection: a Noninvasive Bioluminescence-Imaging Study

“…In nonhuman primates, i.n. delivered wild-type Sendai virus and Sendai virus expressing the HRSV F protein have been shown to protect against HPIV1 and HRSV challenge, with no adverse events (21,58,64). Results on protection from natural reinfection in the present study suggest that an i.m.…”

“…In addition to providing a mouse model to study respiratory paramyxovirus dissemination and pathogenesis, Sendai virus is also a promising Jennerian vaccine candidate against HPIV1 (1,56) and vaccine vector for preclinical HPIV2, HPIV3, and HRSV vaccines (57)(58)(59)(60)(61)(62)(63). There are no confirmed cases of pathogenic Sendai virus infection in humans, and i.n.…”

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

“…In summary, the striking efficacy observed with the systemic DNA prime-tonsillar booster immunization regimen is, to our knowledge, superior to previous studies using DNA of AdV vaccines against hRSV in comparable NHP-animal models (14,15,54) and exhibits levels of viral reduction comparable to that achieved with Sendai virus vaccine or with chimeric parainfluenzavirus expressing hRSV antigens (55)(56)(57). Our results therefore suggest that the novel DNA prime-tonsillar booster regimen is a promising vaccine approach against hRSV and other respiratory viruses that should be pursued further.…”