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

Grünwald, Thomas; Tenbusch, Matthias; Schulte, Reiner; Raue, Katharina; Wolf, Hans; Hannaman, Drew; Swart, Rik L. de; Überla, Klaus; Stahl–Hennig∥, Christiane

doi:10.1128/jvi.02736-13

Cited by 25 publications

(34 citation statements)

References 57 publications

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“…The virus was administered by the intranasal route, which leads to a sustained replication in the nasal cavity in agreement with previous publications (Grunwald et al, 2014;Weltzin et al, 1996) One of our main objectives was to compare the outcome of this infection in different age groups. Indeed, first experimental hRSV infections in macaques were performed in 1977 on newborns (Belshe et al, 1977).…”

Section: Discussionmentioning

confidence: 59%

“…All animals showed some level of viral replication with a peak between days 5 and 9, and resolved the infection. Lung inflammation associated with cellular infiltrates was also observed, except in two reports where animals were infected by the intranasal route (Belshe et al, 1977;Grunwald et al, 2014). These reports thus illustrated that the macaque is an interesting model for preclinical evaluation of vaccines or treatments against hRSV.…”

Section: Introductionmentioning

confidence: 92%

“…This includes mice, cotton rats, guinea pigs, sheep, chinchillas, African green monkeys, macaques and chimpanzees. These different models can be (Belshe et al, 1977;Grunwald et al, 2014;McArthur-Vaughan & Gershwin, 2002;Schmidt et al, 2002;Vaughan et al, 2005;Weltzin et al, 1996), bonnet (Macaca radiata) (Babu et al, 1998;Ponnuraj et al, 2001;Simoes et al, 1999) and cynomolgus monkeys (Macaca fascicularis) (de Swart et al, 2002;de Waal et al, 2004a, b). Experimental designs and major results are summarized in Table 1.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques

Grandin

Lucas‐Hourani

Clavel³

et al. 2015

Journal of General Virology

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There is no large-scale therapy available against human respiratory syncytial virus (hRSV), a major pathogen responsible for acute respiratory diseases. Macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. However, the parameters that influence hRSV growth and control in this model are still poorly understood. We have documented in the following study the influence of age as well as repeated infections on the virological, clinical and immunological parameters of this animal model. Following intranasal inoculation, hRSV replicated in the upper respiratory tract for less than 15 days with no clinical signs regardless of age. Interestingly, we observed the induction of a local immune response at the nasal mucosa as assessed by expression profiles of inflammatory and IFN-stimulated genes. Animals also developed specific antibodies and were immune to reinfection. Thus, we showed that even in infant macaques, intranasal hRSV infection induced both local and systemic immune responses to efficiently control the virus.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques

Grandin

Lucas‐Hourani

Clavel³

et al. 2015

Journal of General Virology

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“…The mouse model has been proven to be semipermissive to RSV and can also be infected efficiently with Sendai virus (45). Recently, virus-vectored vaccines have been administered via different routes, affecting the quality and the quantity of the immune response (20,33,41,42,46). Effective induction of a local immune response could be advantageous in preventing serious infections.…”

Section: Discussionmentioning

confidence: 99%

A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease

Wiegand¹,

Savellini

Papa

et al. 2017

J Virol

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Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCERespiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity and attenuation. We provide a novel RSV vaccine concept based on a genome replication-deficient Sendai vector that has many favorable vaccine characteristics. The specific vaccine design guarantees genetic stability of the transgene; furthermore, it supports a favorable presentation of the antigen, activating the adaptive response, features that other vectored vaccine approaches have often had difficulties with. Wide immunological and pathological analyses in mice confirmed the validity and efficacy of this approach after both parenteral and mucosal administration. Above all, this concept is suitable for initiating clinical studies, and it could also be applied to other infectious diseases.

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“…To induce mucosal immunity against RSV, a DNA vaccine prime ( i.m. , electroporation) and a recombinant adenovirus based-RSV F (tonsillar) prime-boost vaccination strategy was shown to be immunogenic in raising T cell responses and protection in the lower respiratory tract of adult rhesus macaques against RSV challenge [42]. However, recent adenovirus type-5 vector HIV vaccines have failed twice in clinical trials with either the adenovirus vector vaccine itself or as a booster following an initial DNA prime [43].…”

Section: Mucosal Immunization Strategies Against Rsv Infectionmentioning

confidence: 99%

Mucosal vaccines against respiratory syncytial virus

Yang

Varga

2014

Current Opinion in Virology

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Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in infants, young children, immune-compromised and elderly populations worldwide. Natural RSV infection in young children does not elicit long-lasting immunity and individuals remain susceptible to repeated RSV infections throughout life. Because RSV infection is restricted to the respiratory tract, an RSV vaccine should elicit mucosal immunity at upper and lower respiratory tracts in order to most effectively prevent RSV reinfection. Although there is no safe and effective RSV vaccine available, significant progress has been recently made in basic RSV research and vaccine development. This review will discuss recent advances in the identification of a new neutralizing antigenic site within the RSV fusion (F) protein, understanding the importance of mucosal immune responses against RSV infection, and the development of novel mucosal vaccination strategies.

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

Cited by 25 publications

References 57 publications

Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques

Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques

A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease

Mucosal vaccines against respiratory syncytial virus

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