Intranasal proteosome-based respiratory syncytial virus (RSV) vaccines protect BALB/c mice against challenge without eosinophilia or enhanced pathology

Cyr, Sonya; Jones, Trevor O.; Stoica-Popescu, Ioana; Brewer, Angela; Chabot, Sophie; Lussier, Michelle; Burt, David S.; Ward, Brian J.

doi:10.1016/j.vaccine.2007.05.004

Cited by 22 publications

(12 citation statements)

References 51 publications

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“…On the contrary, a properly balanced Th1/Th2 polarization is required for limiting virus replication in the infected tissue and reducing lung pathology. These findings have been confirmed by data obtained from vaccination and virus challenge studies in animal models for RSV .…”

Section: Respiratory Syncytial Virus Immunitysupporting

confidence: 66%

“…Alternatively, formulations consisting of recombinant protein subunits have been increasingly used for vaccine development. These formulations can be applied either alone or in combination with bacterium‐derived or plant‐derived adjuvants to increase viral antigen immunogenicity . Although this approach benefits from increased safety, they may show reduced immunogenicity or unbalanced immune polarization , so they have not been developed further into clinical phases .…”

Section: Therapy and Prophylaxis For Respiratory Syncytial Virusmentioning

confidence: 99%

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Respiratory syncytial virus infection and immunity

González

Bueno

Carreño

et al. 2012

Reviews in Medical Virology

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Respiratory syncytial virus (RSV) is the leading cause for childhood hospitalization and respiratory distress, being recognized as a major health and economic burden worldwide. RSV can exploit host immunity and cause a strong inflammatory response that leads to lung damage and virus dissemination. Unfortunately, the immune response elicited by RSV normally fails to protect against subsequent exposures to the virus. Despite intense research during the 50 years after the discovery of RSV, scientists are just beginning to understand the mechanisms contributing to pathology and to the inadequate immune response shown by susceptible individuals. Here, we discuss some of the most important advances made in this field that could lead to the development of new prophylactic tools. INTRODUCTIONRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children in the world, as well of infant hospitalization due to respiratory disease. In the USA alone, RSV causes approximately 125 000 annual hospitalizations [1]. Because of the high infectivity of the virus, nearly 70% of children are infected by the age of 1 year, whereas almost 100% have been exposed to the virus during their second year of life. Importantly, about 36% of infants under 2 years have suffered at least two infections [2,3]. Although infection rates for RSV are similar throughout the world, severe pathology predominantly occurs in infants displaying risk factors, such as incomplete airway development due to premature birth, pulmonary hypertension, airway hyper-reactivity, congenital heart disease and immunosuppression [4]. Furthermore, RSV-associated acute lower respiratory infection and RSV-associated fatality ratios are higher in infants residing in developing countries [5].Respiratory syncytial virus belongs to the Paramyxoviridae family, which also includes measles, parainfluenza 3, Hendra and Nipah viruses. Together with the recently identified human metapneumovirus, RSV is more specifically classified into the subfamily Pneumovirinae [6]. RSV is an enveloped virus with 10 genes distributed along 15.2 kilobases of negative-stranded RNA that encode 11 proteins (Figure 1). Eight of the RSV proteins are known to be structural and so present in the virion particle (Figure 1). The two non-structural proteins, NS1 and NS2, are expressed only during cell infection and are not packaged into the virion. Whether the M2 gene product, M2-2, is packaged within the virion remains to be determined. Despite extensive research efforts, no vaccines are currently available that are capable of inducing long-lasting protective immunity against this virus. Nevertheless, although a widely used prophylactic strategy based on a humanized neutralizing antibody has been shown to be effective at preventing RSV-induced damage, its high cost has limited the use of this treatment only for high-risk groups, such as preterm infants (<37 weeks of gestational age) and infants suffering from cardiovascular diseases and immunosuppress...

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Section: Respiratory Syncytial Virus Immunitysupporting

confidence: 66%

Section: Therapy and Prophylaxis For Respiratory Syncytial Virusmentioning

confidence: 99%

Respiratory syncytial virus infection and immunity

González

Bueno

Carreño

et al. 2012

Reviews in Medical Virology

View full text Add to dashboard Cite

show abstract

“…Over the last few years, several experimental approaches aimed at developing an effective vaccine against RSV have been designed and assessed, such as attenuated RSV particles (14), recombinant viruses (different from RSV) that express RSV antigens (15)(16)(17), purified RSV proteins administered with bacterial adjuvants (17,18), RSV proteins packed as immune stimulating complexes (19), and RSV sequence peptides applied together with adjuvants (20). Although several RSV vaccine candidates may currently be at the end of their corresponding clinical trials around the world, most of these approaches unfortunately promise to be expensive to the point of being unaffordable for middle/low socioeconomic groups.…”

mentioning

confidence: 99%

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Bueno

González

Cautivo

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

107

155

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“…While formalin-inactivated hRSV vaccine formulations are certainly not currently under consideration for human use, the developers of novel anti-RSV vaccine strategies continue to make a significant effort to demonstrate the absence of hypersensitivity reactions due to the serious nature of this problem [66 - 68]. Given the recent interest in PVM as a model for exploring mechanisms of disease and vaccine strategies, we have established an important point documenting similar immunopathologic responses to both human and mouse pathogens.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Eosinophils and Their Role in Immunopathologic Responses to Formalin-Inactivated Pneumonia Virus of Mice

Percopo

Qiu

Phipps

et al. 2009

The Journal of Immunology

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Enhanced disease is the term used to describe the aberrant Th2-skewed responses to naturally acquired human respiratory syncytial virus (hRSV) infection observed in individuals vaccinated with formalin-inactivated viral Ags. Here we explore this paradigm with pneumonia virus of mice (PVM), a pathogen that faithfully reproduces features of severe hRSV infection in a rodent host. We demonstrate that PVM infection in mice vaccinated with formalin-inactivated Ags from PVM-infected cells (PVM Ags) yields Th2-skewed hypersensitivity, analogous to that observed in response to hRSV. Specifically, we detect elevated levels of IL-4, IL-5, IL-13, and eosinophils in bronchoalveolar lavage fluid of PVM-infected mice that were vaccinated with PVM Ags, but not among mice vaccinated with formalin-inactivated Ags from uninfected cells (control Ags). Interestingly, infection in PVM Ag-vaccinated mice was associated with a ∼10-fold reduction in lung virus titer and protection against weight loss when compared with infected mice vaccinated with control Ags, despite the absence of serum-neutralizing Abs. Given recent findings documenting a role for eosinophils in promoting clearance of hRSV in vivo, we explored the role of eosinophils in altering the pathogenesis of disease with eosinophil-deficient mice. We found that eosinophil deficiency had no impact on virus titer in PVM Ag-vaccinated mice, nor on weight loss or levels of CCL11 (eotaxin-1), IFN-γ, IL-5, or IL-13 in bronchoalveolar lavage fluid. However, levels of both IL-4 and CCL3 (macrophage inflammatory protein-1α) in bronchoalveolar lavage fluid were markedly diminished in PVM Ag-vaccinated, PVM-infected eosinophil-deficient mice when compared with wild-type controls.

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Intranasal proteosome-based respiratory syncytial virus (RSV) vaccines protect BALB/c mice against challenge without eosinophilia or enhanced pathology

Cited by 22 publications

References 51 publications

Respiratory syncytial virus infection and immunity

Respiratory syncytial virus infection and immunity

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Pulmonary Eosinophils and Their Role in Immunopathologic Responses to Formalin-Inactivated Pneumonia Virus of Mice

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