scholarly journals An epitope-specific chemically defined nanoparticle vaccine for respiratory syncytial virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Armando Zuniga ◽  
Oliver Rassek ◽  
Melissa Vrohlings ◽  
Aniebrys Marrero-Nodarse ◽  
Kerstin Moehle ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
The Elderly ◽  
Effective Vaccine ◽  
Lung Pathology ◽  
Nanoparticle Delivery ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Safety Features ◽  
Preclinical Animal Models

AbstractRespiratory syncytial virus (RSV) can cause severe respiratory disease in humans, particularly in infants and the elderly. However, attempts to develop a safe and effective vaccine have so far been unsuccessful. Atomic-level structures of epitopes targeted by RSV-neutralizing antibodies are now known, including that bound by Motavizumab and its clinically used progenitor Palivizumab. We developed a chemically defined approach to RSV vaccine design, that allows control of both immunogenicity and safety features of the vaccine. Structure-guided antigen design and a synthetic nanoparticle delivery platform led to a vaccine candidate that elicits high titers of palivizumab-like, epitope-specific neutralizing antibodies. The vaccine protects preclinical animal models from RSV infection and lung pathology typical of vaccine-derived disease enhancement. The results suggest that the development of a safe and effective synthetic epitope-specific RSV vaccine may be feasible by combining this conformationally stabilized peptide and synthetic nanoparticle delivery system.

Humoral immunity to respiratory syncytial virus in young and elderly adults

2009 ◽  
Vol 137 (12) ◽  
pp. 1684-1686 ◽  
Author(s):  
C. TERROSI ◽  
G. Di GENOVA ◽  
B. MARTORELLI ◽  
M. VALENTINI ◽  
M. G. CUSI
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Age Groups ◽  
The Elderly ◽  
Elderly Subjects ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Relationship Of ◽  
The Relationship

SUMMARYRespiratory syncytial virus (RSV) has been demonstrated to cause substantial disease in elderly and immunocompromised subjects. The relationship of serum antibody to RSV infection and the risk of infection in elderly subjects is controversial, thus we evaluated the presence of neutralizing antibodies to RSV in healthy people of different age groups and the correlation with viral protection. Baseline blood samples from 197 subjects aged 20–80 years were analysed for the presence of anti-RSV antibodies either by indirect immunofluorescence and microneutralization test. The percentage of people who had neutralizing antibodies to RSV was significantly higher (P=0·001) in the youngest group (92·51%) compared to the frail group (36·21%). The RSV antibody level tends to wane in some older people; this factor could determine proneness to RSV re-infections in the elderly who are at a greater risk of developing severe respiratory disease.

scholarly journals A Peptide Mimic of a Protective Epitope of Respiratory Syncytial Virus Selected from a Combinatorial Library Induces Virus-Neutralizing Antibodies and Reduces Viral Load In Vivo

1998 ◽  
Vol 72 (3) ◽  
pp. 2040-2046 ◽  
Author(s):  
Daniel Chargelegue ◽  
Obeid E. Obeid ◽  
Shiou-Chih Hsu ◽  
Michael D. Shaw ◽  
Andrew N. Denbury ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Solid Phase ◽  
Effective Vaccine ◽  
Peptide Mimic ◽  
Rsv Infection ◽  
Multiple Antigen Peptides ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children worldwide. As yet, there is no effective vaccine against RSV infection, and previous attempts to develop a formalin-inactivated vaccine resulted in exacerbated disease in recipients subsequently exposed to the virus. In the work described here, a combinatorial solid-phase peptide library was screened with a protective monoclonal antibody (MAb 19) to identify peptide mimics (mimotopes) of a conserved and conformationally-determined epitope of RSV fusion (F) protein. Two sequences identified (S1 [HWYISKPQ] and S2 [HWYDAEVL]) reacted specifically with MAb 19 when they were presented as solid-phase peptides. Furthermore, after amino acid substitution analyses, three sequences derived from S1 (S1S [HWSISKPQ], S1K [KWYISKPQ], and S1P [HPYISKPQ]), presented as multiple antigen peptides (MAPs), also showed strong reactivity with MAb 19. The affinity constants of the binding of MAb 19, determined by surface plasmon resonance analyses, were 1.19 × 109 and 4.93 × 109 M−1 for S1 and S1S, respectively. Immunization of BALB/c mice with these mimotopes, presented as MAPs, resulted in the induction of anti-peptide antibodies that inhibited the binding of MAb 19 to RSV and neutralized viral infection in vitro, with titers equivalent to those in sera from RSV-infected animals. Following RSV challenge of S1S mimotope-immunized mice, a 98.7% reduction in the titer of virus in the lungs was observed. Furthermore, there was a greatly reduced cell infiltration in the lungs of immunized mice compared to that in controls. These results indicate the potential of peptide mimotopes to protect against RSV infection without exacerbating pulmonary pathology.

scholarly journals Contribution of Dendritic Cells in Protective Immunity against Respiratory Syncytial Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 102 ◽  
Author(s):  
Hi Eun Jung ◽  
Tae Hoon Kim ◽  
Heung Kyu Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Defense Mechanisms ◽  
Adaptive Immune Response ◽  
The Elderly ◽  
Effective Vaccine ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. The socioeconomic burden of RSV infection is substantial because it leads to serious respiratory problems, subsequent hospitalization, and mortality. Despite its clinical significance, a safe and effective vaccine is not yet available to prevent RSV infection. Upon RSV infection, lung dendritic cells (DCs) detecting pathogens migrate to the lymph nodes and activate the adaptive immune response. Therefore, RSV has evolved various immunomodulatory strategies to inhibit DC function. Due to the capacity of RSV to modulate defense mechanisms in hosts, RSV infection results in inappropriate activation of immune responses resulting in immunopathology and frequent reinfection throughout life. This review discusses how DCs recognize invading RSV and induce adaptive immune responses, as well as the regulatory mechanisms mediated by RSV to disrupt DC functions and ultimately avoid host defenses.

scholarly journals Effect of Previous Respiratory Syncytial Virus Infection on Murine Immune Responses to F and G Protein-Containing Virus-Like Particles

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Lori McGinnes Cullen ◽  
Madelyn R. Schmidt ◽  
Trudy G. Morrison
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Immune Memory ◽  
Effective Vaccine ◽  
F Protein ◽  
Virus Like Particles ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTMost individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein-containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV-naive animals. These studies showed that after RSV infection, immunization with a single dose of VLPs containing a conformation-stabilized prefusion F protein stimulated high titers of neutralizing antibodies (NA), while an immunization with post-F-containing VLPs or a second RSV infection only weakly stimulated NA, even though total anti-F protein IgG antibody levels in both VLP-immunized animals were similar. Furthermore, single pre-F or post-F VLP immunization of animals previously infected (primed) with RSV resulted in total anti-F antibody titers that were 10- to 12-fold higher than titers after a VLP prime and boost of RSV-naive animals or after two consecutive RSV infections. The avidities of serum antibodies as well as numbers of splenic B cells and bone marrow cells after different immunization protocols were also assessed. The combined results show that RSV infection can quite effectively prime animals for the production of protective antibodies that can be efficiently activated by a pre-F VLP boost but not by a post-F VLP boost or a second RSV infection.IMPORTANCEHumans may experience repeated infections caused by the same serotype of respiratory syncytial virus (RSV), in contrast to infections with most other viruses, indicating that immune memory responses to RSV are defective. However, the effects of any residual but nonprotective immunity on responses to RSV vaccines are not clear. This study demonstrates that a VLP vaccine candidate containing a stabilized prefusion F protein can robustly stimulate protective immunity in animals previously infected with RSV, while a second RSV infection or a postfusion F-containing VLP cannot. This result shows that a properly constructed immunogen can be an effective vaccine in animals previously infected with RSV. The results also suggest that the defect in RSV memory is not in the induction of that memory but rather in its activation by a subsequent RSV infection.

Interactions between respiratory syncytial virus and the host cell: opportunities for antivirus strategies?

2006 ◽  
Vol 8 (21) ◽  
pp. 1-17 ◽  
Author(s):  
Richard J. Sugrue
Keyword(s):  
Respiratory Syncytial Virus ◽  
Host Cell ◽  
The Elderly ◽  
Paediatric Population ◽  
Health Concern ◽  
Effective Vaccine ◽  
Rsv Infection ◽  
Host Cell Factors ◽  
Syncytial Virus ◽  
Virus Replication Cycle

At the start of the 21st century, respiratory syncytial virus (RSV) remains a serious global health concern. Although RSV has traditionally been acknowledged as a leading cause of morbidity and mortality in the paediatric population, the elderly and people with suppressed immune systems are now also recognised as being at risk from serious RSV infection. This problem is currently exacerbated by the lack of an effective vaccine to prevent RSV infection. Although the virus proteins play a variety of roles during the virus replication cycle, in many cases these tasks are performed via specific interactions with host-cell factors, including proteins, carbohydrates and lipids. The way in which RSV interacts with the host cell is currently being examined using a battery of different techniques, which encompass several scientific disciplines. This is providing new and interesting insights into how RSV interacts with the host cell at the molecular level, which in turn is offering the hope of new strategies to prevent RSV infection.

scholarly journals Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus.

1988 ◽  
Vol 168 (3) ◽  
pp. 1163-1168 ◽  
Author(s):  
M J Cannon ◽  
P J Openshaw ◽  
B A Askonas
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cell Line ◽  
Respiratory Disease ◽  
Cytotoxic T Cells ◽  
Lung Pathology ◽  
Class I Mhc ◽  
Rsv Infection ◽  
Syncytial Virus

We have examined the function of class I MHC-restricted cytotoxic T cells in experimental respiratory syncytial virus (RSV) infection of BALB/c mice by transfer of T cell line MJC-A2 and CTL clone E8a into RSV-infected mice. The T cell line cleared pulmonary RSV infection within 5 d in persistently infected gamma-irradiated mice, but caused acute respiratory disease. This was only seen in infected mice and was often lethal after transfer of greater than 3 x 10(6) CTL. Lower numbers of CTL produced less severe disease but still cleared lung RSV, albeit over a longer time course (up to 10 d). Clearance of lung RSV in immunocompetent mice by the T cell line and CTL clone was again accompanied by acute and sometimes lethal respiratory disease. Bronchoalveolar lavage showed severe lung hemorrhage and frequent neutrophil efflux in mice with CTL-augmented disease.

scholarly journals Chemokine regulation of inflammation during respiratory syncytial virus infection

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1837 ◽  
Author(s):  
Rinat Nuriev ◽  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Infection Process ◽  
Viral Control ◽  
Small Proteins ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Developed World ◽  
Immune Detection

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections especially in infants, immunocompromised individuals and the elderly and is the most common cause of infant hospitalisation in the developed world. The immune responses against RSV are crucial for viral control and clearance but, if dysregulated, can also result in immunopathology and impaired gas exchange. Lung immunity to RSV and other respiratory viruses begins with the recruitment of immune cells from the bloodstream into the lungs. This inflammatory process is controlled largely by chemokines, which are small proteins that are produced in response to innate immune detection of the virus or the infection process. These chemokines serve as chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes. In this review, we highlight recent advances in the field of RSV infection and disease, focusing on how chemokines regulate virus-induced inflammation.

scholarly journals Lentiviral and AAV-mediated Expression of Palivizumab Offer protection against Respiratory Syncytial Virus infection

2021 ◽  
Author(s):  
Agata Antepowicz ◽  
Omar Habib ◽  
Freja Kirsebom ◽  
Cecilia Johansson ◽  
Deborah R. Gill ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vulnerable Populations ◽  
The Elderly ◽  
Complete Protection ◽  
Adeno Associated Virus ◽  
Common Cause ◽  
Immunodeficiency Virus ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations.

scholarly journals Antibiotic Minocycline Prevents Respiratory Syncytial Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 739 ◽  
Author(s):  
Swapnil S. Bawage ◽  
Pooja M. Tiwari ◽  
Shreekumar Pillai ◽  
Vida A. Dennis ◽  
Shree R. Singh
Keyword(s):  
Respiratory Syncytial Virus ◽  
Specific Activity ◽  
The Body ◽  
Effective Vaccine ◽  
Mortality And Morbidity ◽  
Viral Activity ◽  
Immunodeficiency Virus ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Common Respiratory Virus

Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known to show anti-viral activity against Influenza virus, Japanese encephalitis virus, Simian immunodeficiency virus, Human immunodeficiency virus and West Nile virus. Here, we investigate the effect of minocycline on Respiratory syncytial virus (RSV), a common respiratory virus that causes severe mortality and morbidity in infants, children, and older adult populations. Currently, there is no effective vaccine or treatment for RSV infection; hence, there is a critical need for alternative and effective drug choices. Our study shows that minocycline reduces the RSV-mediated cytopathic effect and prevents RSV infection. This is the first study demonstrating the anti-viral activity of minocycline against RSV.

scholarly journals Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection

2015 ◽  
Vol 59 (8) ◽  
pp. 4889-4900 ◽  
Author(s):  
Robert Jordan ◽  
Matt Shao ◽  
Richard L. Mackman ◽  
Michel Perron ◽  
Tomas Cihlar ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Structural Analog ◽  
Therapeutic Benefit ◽  
Viral Envelope ◽  
Fusion Inhibitor ◽  
Lung Pathology ◽  
Host Cell Membrane ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV.

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