Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

Pierantoni, Angiolo; Esposito, Maria Teresa; Ammendola, Virginia; Napolitano, Federico; Grazioli, Fabiana; Abbate, Adele; Sorbo, Mariarosaria Del; Siani, Loredana; D’Alise, Anna Morena; Taglioni, Alessandra; Perretta, Gemma; Siccardi, Antonio G.; Soprana, Elisa; Panigada, Maddalena; Thom, Michelle; Scarselli, Elisa; Folgori, Antonella; Colloca, Stefano; Taylor, Geraldine; Cortese, Riccardo; Nicosia, Alfredo; Capone, Stefania; Vitelli, Alessandra

doi:10.1038/mtm.2015.18

Cited by 47 publications

(61 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While there is significant evidence that live RSV infection actively prevents the development of a proper RSVspecific CD8 ϩ T cell response, most probably through nonstructural viral factors (47)(48)(49)(50)(51), it has been shown in vaccine studies that a specific CTL response can contribute to protection against RSV when properly induced, such as through virus-vectored vaccines (33,42,(51)(52)(53)(54). In the present study, the SeV76-vectored vaccine induced a clear cell-mediated immune response in animals.…”

Section: Discussionmentioning

confidence: 52%

“…Current RSV vaccine candidates often express the F protein in a secreted version, due to its capacity to stimulate a protective immune response, or as an additional surface protein embedded in the envelopes of virus-vectored vaccines (9,12,33,41,42). The latter is particularly efficient, since it makes the vaccine more immunogenic for RSV, thus contributing to its efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…mucosal immunization can trigger humoral and cell-mediated immunity both at mucosal sites and systemically (Brandtzaeg, 2010;Holmgren & Czerkinsky, 2005). The presence of high levels of IgAs in nasal lymphoid tissue and in the lungs, which are the respiratory pathways through which OPVXs infect animals and humans, can be fundamental for inhibition of viral attachment to the mucosal epithelium, and provide protection from infection (Pierantoni et al, 2015). Finally, i.n.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

et al. 2016

View full text Add to dashboard Cite

Please cite this article as: Bissa, M., Quaglino, E., Zanotto, C., Illiano, E., Rolih, V., Pacchioni, S., Cavallo, F., De Giuli Morghen, C., Radaelli, A., Protection of mice against the highly pathogenic VV IHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity, Antiviral Research (2016Research ( ), doi: 10.1016Research ( / j.antiviral.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VV IHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27antibodies and IFNγ-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VV IHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/ boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/ intranasal administration routes contributed to effective immune responses and mouse survival.

show abstract

“…Because studies with other virus-vectored vaccines have shown that heterologous prime/boost with ChAd and modified vaccinia Ankara (MVA) is more immunogenic than homologous prime/boost regimens in phase 1 and 2a human clinical trials (15,16), we constructed an MVA encoding the same HRSV antigen, consisting of secreted F, N, and M2-1 (MVA-RSV), and showed that in nonhuman primates, it could effectively boost humoral and cellular responses primed by PanAd3-RSV, and induce mucosal antibodies when the priming dose was delivered IN (14). However, a pediatric vaccine based on heterologous prime/boost can pose serious challenges to clinical development in terms of large-scale manufacturing and, most importantly, safety.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

Taylor

Thom

Capone³

et al. 2015

Sci. Transl. Med.

Self Cite

View full text Add to dashboard Cite

Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man.

show abstract

Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

Cited by 47 publications

References 50 publications

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

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

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

Contact Info

Product

Resources

About