Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection

Ivanov, V. A.; Oomens, Antonius G. P.; Papin, James F.; Staats, R; Reuter, Darlene; Yu, Zhongxin; Piedra, Pedro A.; Wellliver, Robert C.

doi:10.1016/j.vaccine.2021.06.013

Cited by 6 publications

(8 citation statements)

References 22 publications

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“…route compared with the i.n. route in baboons 32 . Moreover, a pharmacokinetic study in mice showed that i.n.…”

Section: Discussionmentioning

confidence: 99%

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques

McMahan,

Wegmann,

Aid

et al. 2023

Nature

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A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants1,2, although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent3–7, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8+ and CD4+ T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.

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“…route compared with the i.n. route in baboons 32 . Moreover, a pharmacokinetic study in mice showed that i.n.…”

Section: Discussionmentioning

confidence: 99%

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques

McMahan,

Wegmann,

Aid

et al. 2023

Nature

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“…The M protein drives the coordination between viral structural components and accelerates virus assembly by connecting the nucleocapsid and lipid bilayer envelope ( 60 , 62 ). The M protein is in charge of reconstituting other synthetic viral proteins into a new and complete virus ( 63 ). Therefore, in the absence of the M protein, recombination would not take place RSV virus will not replicate ( 63 , 64 ).…”

Section: Discussionmentioning

confidence: 99%

“…The M protein is in charge of reconstituting other synthetic viral proteins into a new and complete virus ( 63 ). Therefore, in the absence of the M protein, recombination would not take place RSV virus will not replicate ( 63 , 64 ). Our work revealed that the effect of baicalin on the inhibiting translation of the M RNA—which was the limiting factor for RSV replication—was mediated by the release of L13a from the large ribosome.…”

Section: Discussionmentioning

confidence: 99%

Baicalin Induces a Potent Innate Immune Response to Inhibit Respiratory Syncytial Virus Replication via Regulating Viral Non-Structural 1 and Matrix RNA

Qin

Huang

2022

Front. Immunol.

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Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10−5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection.

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“…Recently, Ivanov et al . demonstrated that intranasal and intrapulmonary administrations of M-protein deleted RSV vaccine in infant baboons was effective to alleviate clinical symptoms and reduce viral replication after RSV challenge [ 116 ]. The neutralising antibodies response after intrapulmonary vaccination (4–6 months) was stronger compared to intranasal vaccination (1 month).…”

Section: Inhalation Nanotherapies For Viral Respiratory Infectionsmentioning

confidence: 99%

“…The neutralising antibodies response after intrapulmonary vaccination (4–6 months) was stronger compared to intranasal vaccination (1 month). Their results showed that intrapulmonary vaccination appeared more effective to prevent tachypnea and to reduce work of breathing and viral replication in infant baboons [ 116 ]. In another study, long term memory immune response (15 months duration of RSV-specific neutralising antibody) in mice was induced following the single dose intranasal administration of a virus-like particle (VLP) containing recombinant matrix protein (M) and F-glycoprotein of RSV [ 117 ].…”

Section: Inhalation Nanotherapies For Viral Respiratory Infectionsmentioning

confidence: 99%

Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

2023

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With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.

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Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection

Cited by 6 publications

References 22 publications

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques

Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques

Baicalin Induces a Potent Innate Immune Response to Inhibit Respiratory Syncytial Virus Replication via Regulating Viral Non-Structural 1 and Matrix RNA

Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

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