scholarly journals The Immunogenicity and Safety of Rsv Vaccines in Development: A Systematic Review

2020 ◽  
Author(s):  
Jing Shan
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Respiratory Syncytial Virus ◽  
Pregnant Women ◽  
Vaccine Candidate ◽  
Controlled Vocabulary ◽  
Acute Lower Respiratory Infection ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccines in pipeline to prevent it but a systematic review on immunogenicity and safety of vaccine is lacking. Methods: This systematic review of RSV vaccine clinical trials was undertaken using 4 databases. Searches were conducted using both controlled vocabulary terms such as ‘Respiratory Syncytial Virus, Human’, ‘Respiratory Syncytial Virus Infections’, ‘Respiratory Syncytial Virus Vaccines’, ‘Immunization’, ‘Immunization Programs’ and ‘Vaccines’ and corresponding text word terms. The searches for published papers were limited to clinical trials published from January 2000 to August 6th, 2018. RSV infection case was defined as RSV associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically-confirmed test (Western Blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. Results: Of 4395 publications, 24 were included and data were extracted covering 4 major types of RSV vaccine candidates, these being live-attenuated/chimeric (n=9), recombinant-vector (n=10), subunit (n=1) and nanoparticle vaccines (n=4). For RSV infection cases, 7 trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. Conclusion: LID ∆M2-2, MEDI M2-2, and RSVcps2 (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate was considered as a potential effective vaccine. Although no promising vaccine was identified from pregnant-women test, RSV F-024 subunit vaccine candidate and an RSV F nanoparticle vaccine showed encouraging results in healthy non-pregnant women.

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

The burden of Respiratory Syncytial Virus (RSV) infection in the Middle East and North Africa (MENA) region across age groups: A systematic review

Vaccine ◽  
2021 ◽  
Author(s):  
Yolla Youssef ◽  
Ahmad Chmaisse ◽  
Celina Boutros ◽  
Sarah Chamseddine ◽  
Danielle Fayad ◽  
...  
Keyword(s):  
Systematic Review ◽  
Respiratory Syncytial Virus ◽  
Middle East ◽  
North Africa ◽  
Age Groups ◽  
Mena Region ◽  
Rsv Infection ◽  
Syncytial Virus

scholarly journals Pulmonary Susceptibility of Neonates to Respiratory Syncytial Virus Infection: A Problem of Innate Immunity?

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Carole Drajac ◽  
Daphné Laubreton ◽  
Sabine Riffault ◽  
Delphyne Descamps
Keyword(s):  
Respiratory Syncytial Virus ◽  
Early Period ◽  
Epidemiological Studies ◽  
Cell Immune Response ◽  
Acute Lower Respiratory Infection ◽  
Viral Agent ◽  
Rsv Infection ◽  
Immunological Factors ◽  
Syncytial Virus ◽  
Severity Of The Disease

Human respiratory syncytial virus (RSV) is a common and highly contagious viral agent responsible for acute lower respiratory infection in infants. This pathology characterized by mucus hypersecretion and a disturbed T cell immune response is one of the major causes of infant hospitalization for severe bronchiolitis. Although different risk factors are associated with acute RSV bronchiolitis, the immunological factors contributing to the susceptibility of RSV infection in infants are not clearly elucidated. Epidemiological studies have established that the age at initial infection plays a central role in the severity of the disease. Thus, neonatal susceptibility is intrinsically linked to the immunological characteristics of the young pulmonary mucosa. Early life is a critical period for the lung development with the first expositions to external environmental stimuli and microbiota colonization. Furthermore, neonates display a lung immune system that profoundly differs to those from adults, with the predominance of type 2 immune cells. In this review, we discuss the latest information about the lung immune environment in the early period of life at a steady state and upon RSV infection and how we can modulate neonatal susceptibility to RSV infection.

scholarly journals Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease

2015 ◽  
Vol 23 (3) ◽  
pp. 189-195 ◽  
Author(s):  
Patricio L. Acosta ◽  
Mauricio T. Caballero ◽  
Fernando P. Polack
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Disease ◽  
Wild Type Virus ◽  
Wild Type ◽  
T Helper ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Complex Deposition

ABSTRACTIn 1967, infants and toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (RSV) experienced an enhanced form of RSV disease characterized by high fever, bronchopneumonia, and wheezing when they became infected with wild-type virus in the community. Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a “peribronchiolar monocytic infiltration with some excess in eosinophils.” Decades of research defined enhanced RSV disease (ERD) as the result of immunization with antigens not processed in the cytoplasm, resulting in a nonprotective antibody response and CD4+T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection. In recent years, the field of RSV experienced significant changes. Numerous vaccine candidates with novel designs and formulations are approaching clinical trials, defying our previous understanding of favorable parameters for ERD. This review provides a succinct analysis of these parameters and explores criteria for assessing the risk of ERD in new vaccine candidates.

scholarly journals Prevalence and Risk Factors of Respiratory Syncytial Virus in Children under 5 Years of Age in the WHO European Region: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (5) ◽  
pp. 416
Author(s):  
Nora Suleiman-Martos ◽  
Alberto Caballero-Vázquez ◽  
Jose Luis Gómez-Urquiza ◽  
Luis Albendín-García ◽  
Jose Luis Romero-Béjar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Respiratory Syncytial Virus ◽  
Meta Analysis ◽  
World Health ◽  
European Region ◽  
Healthy Children ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Children Under 5

A respiratory syncytial virus (RSV) is the major cause of respiratory tract infection in children under 5 years. However, RSV infection in the European Region of the World Health Organization has not been systematically reviewed. The aim was to determine the prevalence and factors associated with RSV in children under 5 years of age in European regions. A systematic review and meta-analysis was performed. CINAHL, Medline, LILACS, ProQuest, SciELO, and Scopus databases were consulted for studies published in the last 5 years, following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The search equation was “respiratory syncytial virus AND (newborn OR infant OR child) AND (prevalence OR risk factors)”. Studies reporting the prevalence of RSV were eligible for inclusion in the meta-analysis. A total of 20 articles were included. The meta-analytic prevalence estimation of RSV, with a sample of n = 16,115 children, was 46% (95% CI 34–59%). The main risk factors were age, male gender, winter season, and environmental factors such as cold temperatures, higher relative humidity, high concentrations of benzene, exposure to tobacco, and living in urban areas. Robust age-specific estimates of RSV infection in healthy children should be promoted in order to determine the optimal age for immunization. In addition, it is necessary to analyse in greater depth the potentially predictive factors of RSV infection, to be included in prevention strategies.

scholarly journals Recombinant Respiratory Syncytial Virus (RSV) Bearing a Set of Mutations from Cold-Passaged RSV Is Attenuated in Chimpanzees

1998 ◽  
Vol 72 (5) ◽  
pp. 4467-4471 ◽  
Author(s):  
Stephen S. Whitehead ◽  
Katalin Juhasz ◽  
Cai-Yen Firestone ◽  
Peter L. Collins ◽  
Brian R. Murphy
Keyword(s):  
Respiratory Syncytial Virus ◽  
Recombinant Virus ◽  
Wild Type Strain ◽  
Nucleotide Sequence Analysis ◽  
Missense Mutations ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT A set of five missense mutations previously identified by nucleotide sequence analysis of subgroup A cold-passaged (cp) respiratory syncytial virus (RSV) has been introduced into a recombinant wild-type strain of RSV. This recombinant virus, designated rA2cp, appears to replicate less efficiently in the upper and lower respiratory tracts of seronegative chimpanzees than either biologically derived or recombinant wild-type RSV. Infection with rA2cp also resulted in significantly less rhinorrhea and cough than infection with wild-type RSV. These findings confirm the role of thecp mutations in attenuation of RSV and identify their usefulness for inclusion in future live attenuated recombinant RSV vaccine candidates.

scholarly journals Association Between Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection in Early Life and Recurrent Wheeze and Asthma in Later Childhood

2019 ◽  
Vol 222 (Supplement_7) ◽  
pp. S628-S633 ◽  
Author(s):  
Ting Shi ◽  
Yujing Ooi ◽  
Ei Mon Zaw ◽  
Natasa Utjesanovic ◽  
Harry Campbell ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Early Life ◽  
Subsequent Development ◽  
Respiratory Morbidity ◽  
Acute Lower Respiratory Infection ◽  
High Risk Population ◽  
Rsv Infection ◽  
Recurrent Wheeze ◽  
Syncytial Virus

Abstract Background Recurrent wheeze and asthma in childhood are commons causes of chronic respiratory morbidity globally. We aimed to explore the association between respiratory syncytial virus (RSV) infection in early life and subsequent respiratory sequelae up to age 12 years. Methods We estimated the strength of association by 3 control groups and 3 follow-up age groups, with data from studies published between January 1995 and May 2018. We also estimated associations by diagnostic criteria, age at infection, and high-risk population. Results Overall, we included 41 studies. A statistically significant association was observed between early life RSV infection and subsequent childhood recurrent wheeze, in comparison to those who were healthy or those without respiratory symptoms: OR 3.05 (95% confidence interval [CI], 2.50–3.71) for 0 to <36 months follow-up age; OR 2.60 (95% CI, 1.67–4.04) for 36–72 months; and OR 2.14 (95% CI, 1.33–3.45) for 73–144 months. For the subsequent development of asthma, a statistically significant association was observed only in relation to those aged 73–144 months at follow-up: OR 2.95 (95% CI, 1.96–4.46). Conclusions Further studies using standardized definitions and from diverse settings are needed to elucidate the role of confounders and provide more robust estimates.

scholarly journals Parainfluenza Virus 5 Expressing Wild-Type or Prefusion Respiratory Syncytial Virus (RSV) Fusion Protein Protects Mice and Cotton Rats from RSV Challenge

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Shannon I. Phan ◽  
James R. Zengel ◽  
Huiling Wei ◽  
Zhuo Li ◽  
Dai Wang ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Fusion Protein ◽  
Vaccine Candidate ◽  
Parainfluenza Virus ◽  
Wild Type ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Parainfluenza Virus 5 ◽  
Syncytial Virus ◽  
Vectored Vaccine

ABSTRACT Human respiratory syncytial virus (RSV) is the leading cause of pediatric bronchiolitis and hospitalizations. RSV can also cause severe complications in elderly and immunocompromised individuals. There is no licensed vaccine. We previously generated a parainfluenza virus 5 (PIV5)-vectored vaccine candidate expressing the RSV fusion protein (F) that was immunogenic and protective in mice. In this work, our goal was to improve the original vaccine candidate by modifying the PIV5 vector or by modifying the RSV F antigen. We previously demonstrated that insertion of a foreign gene at the PIV5 small hydrophobic (SH)–hemagglutinin-neuraminidase (HN) junction or deletion of PIV5 SH increased vaccine efficacy. Additionally, other groups have demonstrated that antibodies against the prefusion conformation of RSV F have more potent neutralizing activity than antibodies against the postfusion conformation. Therefore, to improve on our previously developed vaccine candidate, we inserted RSV F at the PIV5 SH-HN gene junction or used RSV F to replace PIV5 SH. We also engineered PIV5 to express a prefusion-stabilized F mutant. The candidates were tested in BALB/c mice via the intranasal route and induced both humoral and cell-mediated immunity. They also protected against RSV infection in the mouse lung. When they were administered intranasally or subcutaneously in cotton rats, the candidates were highly immunogenic and reduced RSV loads in both the upper and lower respiratory tracts. PIV5-RSV F was equally protective when administered intranasally or subcutaneously. In all cases, the prefusion F mutant did not induce higher neutralizing antibody titers than wild-type F. These results show that antibodies against both pre- and postfusion F are important for neutralizing RSV and should be considered when designing a vectored RSV vaccine. The findings also that indicate PIV5-RSV F may be administered subcutaneously, which is the preferred route for vaccinating infants, who may develop nasal congestion as a result of intranasal vaccination. IMPORTANCE Despite decades of research, human respiratory syncytial virus (RSV) is still a major health concern for which there is no vaccine. A parainfluenza virus 5-vectored vaccine expressing the native RSV fusion protein (F) has previously been shown to confer robust immunity against RSV infection in mice, cotton rats, and nonhuman primates. To improve our previous vaccine candidate, we developed four new candidates that incorporate modifications to the PIV5 backbone, replace native RSV F with a prefusion-stabilized RSV F mutant, or combine both RSV F and PIV5 backbone modifications. In this work, we characterized the new vaccine candidates and tested their efficacies in both murine and cotton rat models of RSV infection. Most importantly, we found that PIV5-based RSV vaccine candidates were efficacious in preventing lower respiratory tract infection as well as in reducing the nasal viral load when administered via the subcutaneous route.

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