Respiratory syncytial virus vaccine: where are we now and what comes next?

Noor, Asif; Krilov, Leonard R.

doi:10.1080/14712598.2018.1544239

Cited by 30 publications

(29 citation statements)

References 62 publications

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“…The optimal type of RSV vaccine employed, i.e., RSV F and/or G protein, will likely be dependent on the host target population (162, 163), with four groups being of interest: (1) infants and young children, (2) adults, (3) the elderly, and (4) pregnant woman. Immunization schedule (prime/boost) and the specific platform for delivery of the vaccine are also likely to be important (162, 164, 165). Consequently, there are a spectrum of RSV vaccines being tested that include live-attenuated and chimeric virus, purified F protein (including variants engineered to present predominantly the pre-fusion conformation), particle and vector-based presentations of the antigen(s) (165).…”

Section: Introductionmentioning

confidence: 99%

“…Immunization schedule (prime/boost) and the specific platform for delivery of the vaccine are also likely to be important (162, 164, 165). Consequently, there are a spectrum of RSV vaccines being tested that include live-attenuated and chimeric virus, purified F protein (including variants engineered to present predominantly the pre-fusion conformation), particle and vector-based presentations of the antigen(s) (165). For example, RSV F protein particle-based (Novovax) (166, 167) and RSV F subunit (GSK; NIH) vaccines are being evaluated for use in pregnant mothers, while RSV F protein particle-based (Novovax; Mucosis) and live-attenuated vaccines such as RSV deletion mutant vaccines, e.g., ΔM2-2 and ΔNS2 constructs (Sanofi; NIH) are being targeted for the pediatric population with potential extension to older children and young adults (168).…”

Section: Introductionmentioning

confidence: 99%

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Role of Type I Interferon (IFN) in the Respiratory Syncytial Virus (RSV) Immune Response and Disease Severity

et al. 2019

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Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in children <2 years of age. Increased morbidity and mortality have been reported in high-risk patients, such as premature infants, patients with cardiac disease, and severely immune compromised patients. Severe disease is associated with the virulence of the virus as well as host factors specifically including the innate immune response. The role of type I interferons (IFNs) in the response to RSV infection is important in regulating the rate of virus clearance and in directing the character of the immune response, which is normally associated with protection and less severe disease. Two RSV non-structural proteins, NS1 and NS2, as well as the envelope G glycoprotein are known to suppress type I IFN production and a robust type I IFN response to RSV does not occur in human infants or neonatal mouse models of RSV infection. Additionally, presence of type I IFNs are associated with mild symptoms in infants and administration of IFN-α prior to infection of neonatal mice with RSV reduces immunopathology. This evidence has driven RSV prophylaxis and therapeutic efforts to consider strategies for enhancing type I IFN production.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Type I Interferon (IFN) in the Respiratory Syncytial Virus (RSV) Immune Response and Disease Severity

et al. 2019

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“…The small reduction in childhood influenza-related deaths from 30 cases during 2003–05 to 20 in 2013–15 could be due to the programme, but numbers are too small for formal statistical analysis. In addition to currently available vaccines,16 investigational vaccines that have the potential to reduce infectious disease burden and associated deaths, include the antenatal GBS vaccine,17 and several RSV vaccines across the life-course 18…”

Section: Discussionmentioning

confidence: 99%

Infection is associated with one in five childhood deaths in England and Wales: analysis of national death registrations data, 2013–15

et al. 2020

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ObjectiveTo estimate the contribution of infections to childhood deaths in England and Wales over a 3-year period.DesignRetrospective analysis of national electronic death registration data.SettingEngland and Wales.PatientsChildren aged 28 days to 15 years who died during 2013–15.Main outcome measuresThe proportion of children who died of infection compared with total deaths over 3 years; the main pathogens responsible for infection-related deaths in different age groups; comparison with similar data from 2003 to 2005.ResultsThere were 5088 death registrations recorded in children aged 28 days to <15 years in England and Wales during the three calendar years, 2013–2015 (17.6 deaths/100 000 children annually) compared with 6897 (23.9/100 000) during 2003–05 (incidence rate ratios (IRR) 0.74, 95% CI 0.71 to 0.77). During 2013–15, there were 951 (18.7%, 951/5088) infection-related deaths compared with 1368 (19.8%, 1368/6897) during 2003–05, equivalent to an infection-related mortality rate of 3.3/100 000 compared with 4.8/100 000 during the two periods (IRR 0.69, 95% CI 0.64 to 0.75), respectively. An underlying comorbidity was recorded in 55.0% (523/951) of death registrations during 2013–15 and increased with age. Where recorded, respiratory tract infection was the most commonly reported presentation (374/876, 42.7%) during 2013–15. Central nervous system infections accounted for only 4.8% (42/876). Overall, 63.1% (378/599) of infection-related deaths were associated with a bacterial, 34.2% (205/599) with a viral and 2.5% (15/599) with a fungal infection.ConclusionsBeyond the neonatal period, all-cause and infection-related childhood mortality rates have declined by 26% and 31%, respectively, over the past decade. However, infection continues to contribute to one in five childhood deaths.

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“…However, a RSV vaccine remains an unmet need, and there has been a long track record of vaccine candidates failing to elicit consistent immune responses which translate to a sufficient levels of protection across the population. 3 Furthermore, serious vaccine enhanced disease (VED) was observed in some infants immunized with the formalin-inactivated RSV vaccine. 4 Thus, a strategy which bypasses the requirement to engage the host immune system would be very attractive.…”

Section: Introductionmentioning

confidence: 99%

Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity

Schultheis

Pugh

et al. 2020

Human Vaccines & Immunotherapeutics

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Respiratory Syncytial virus (RSV) is a major threat to many vulnerable populations. There are currently no approved vaccines, and RSV remains a high unmet global medical need. Here we describe the employment of a novel synthetic DNA-encoded antibody technology platform to develop and deliver an engineered human DNA-encoded monoclonal antibody (dMAb TM ) targeting the fusion protein (F) of RSV as a new approach to prevention or therapy of at risk populations. In in vivo models, a single administration of synthetic DNA-encoding the single-chain fragment variable-constant fragment (scFv-Fc) RSV-F dMAb resulted in robust and durable circulating levels of a functional antibody systemically and in mucosal tissue. In cotton rats, which are the gold-standard animals to model RSV infection, we observed sustained scFv-Fc RSV-F dMAb in the sera and lung-lavage samples, demonstrating the potential for both long-lasting immunity to RSV and effective biodistribution. The scFv-Fc RSV-F dMAb harbored in the sera exhibited RSV antigen-specific binding and potent viral neutralizing activity. Importantly, in vivo delivery of synthetic DNA-encoding, the scFv-Fc RSV-F dMAb protected animals against viral challenge. Our findings support the significance of dMAbs as a potential platform technology for durable protection against RSV disease.

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Respiratory syncytial virus vaccine: where are we now and what comes next?

Cited by 30 publications

References 62 publications

Role of Type I Interferon (IFN) in the Respiratory Syncytial Virus (RSV) Immune Response and Disease Severity

Role of Type I Interferon (IFN) in the Respiratory Syncytial Virus (RSV) Immune Response and Disease Severity

Infection is associated with one in five childhood deaths in England and Wales: analysis of national death registrations data, 2013–15

Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity

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