Potentiating Lung Mucosal Immunity Through Intranasal Vaccination

Nelson, Shakira M.; Sant, Andrea J.

doi:10.3389/fimmu.2021.808527

Cited by 10 publications

(6 citation statements)

References 102 publications

(142 reference statements)

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“…These tissue-resident memory T cells contribute to mucosal protective immunity [ 44 , 45 ]. Tissue-resident memory T cells in the lung mucosa have been reported to mediate site-specific viral clearance and protection from a lethal viral challenge [ 46 , 47 , 48 ]. To assess whether the IN-Fos47 generates tissue-specific T cell immunity in the lung mucosa, lymphocytes were isolated from the lungs of IN-boosted mice on day 35 (1 week after the last boosting) and analyzed by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination

et al. 2022

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Systemically vaccinated individuals against COVID-19 and influenza may continue to support viral replication and shedding in the upper airways, contributing to the spread of infections. Thus, a vaccine regimen that enhances mucosal immunity in the respiratory mucosa is needed to prevent a pandemic. Intranasal/pulmonary (IN) vaccines can promote mucosal immunity by promoting IgA secretion at the infection site. Here, we demonstrate that an intramuscular (IM) priming-IN boosting regimen with an inactivated influenza A virus adjuvanted with the liposomal dual TLR4/7 adjuvant (Fos47) enhances systemic and local/mucosal immunity. The IN boosting with Fos47 (IN-Fos47) enhanced antigen-specific IgA secretion in the upper and lower respiratory tracts compared to the IM boosting with Fos47 (IM-Fos47). The secreted IgA induced by IN-Fos47 was also cross-reactive to multiple influenza virus strains. Antigen-specific tissue-resident memory T cells in the lung were increased after IN boosting with Fos47, indicating that IN-Fos47 established tissue-resident T cells. Furthermore, IN-Fos47 induced systemic cross-reactive IgG antibody titers comparable to those of IM-Fos47. Neither local nor systemic reactogenicity or adverse effects were observed after IN delivery of Fos47. Collectively, these results indicate that the IM/IN regimen with Fos47 is safe and provides both local and systemic anti-influenza immune responses.

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Section: Resultsmentioning

confidence: 99%

A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination

et al. 2022

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“…However, advances in vaccine production technology are expected to lead to a shift to more selective antigens, such as protein and mRNA vaccine ( 45 ), and the combination of these vaccines and laser adjuvants should also be considered. Additionally, recent studies have suggested that mucosal immunization with intranasal influenza live attenuated vaccines may enhance the response of tissue resident B and T cells in the respiratory tract ( 46 ), and the application of this technology in these new administration routes is also expected.…”

Section: Discussionmentioning

confidence: 99%

1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines

et al. 2022

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With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light to elicit an adjuvant effect, referred to as “laser adjuvant.” We have been investigating the mechanism of laser adjuvant in influenza mouse models using noninvasive continuous-wave (CW) near-infrared (NIR) light mainly at a wavelength of 1064 nm, and have shown that the production of reactive-oxygen-species (ROS) in the skin and mast cells in the skin tissue plays an important role in the laser adjuvant effect. The new wavelength of 1270 nm NIR light is characterized by its ability to elicit the same vaccine adjuvant effect as other wavelengths at a lower energy, and may be suitable for clinical applications. In this study, we investigated the physiological activity of CW1270 nm NIR light in mast cells, its biological activity on mouse skin, and the durability of the vaccine adjuvant effect in influenza vaccine mouse models. We show that irradiation of mast cells with 1270 nm NIR light produced ROS and ATP, and irradiation of isolated mitochondria also produced ATP. In mouse skin, the relative expression levels of chemokine mRNAs, such as Ccl2 and Ccl20, were increased by irradiation with 1270 and 1064 nm NIR light at minimum safe irradiance. However, the relative expression of Nfkb1 was increased at 1064 nm, but not at 1270 nm. Serum anti-influenza IgG antibody titers increased early after immunization with 1064 nm, whereas with 1270 nm, there was not only an early response of antibody production but also persistence of antibody titers over the medium- to long-term. Thus, to our knowledge, we show for the first time that 1270 nm NIR light induces ROS and ATP production in mitochondria as photoreceptors, initiating a cascade of laser adjuvant effects for intradermal vaccines. Additionally, we demonstrate that there are wavelength-specific variations in the mechanisms and effects of laser adjuvants. In conclusion, CW1270 nm NIR light is expected to be clinically applicable as a novel laser adjuvant that is equivalent or superior to 1064 nm NIR light, because it can be operated at low energy and has a wavelength-specific adjuvant effect with medium- to long-lasting antibody titer.

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“…The advantages of the rNDV vaccine platform and delivery route used in the present study are the following. Intranasal administration of modified live virus vaccines has been shown to induce mucosal immune responses and local delivery of antigen necessary to activate lung lymphocyte subpopulations and establish resident memory within the respiratory tract 34 , thereby protecting against the virus at its site of entry. Secondly, rNDV-vectored vaccines can be grown in embryonated eggs, using the same manufacturing methods and facilities as used to produce the seasonal influenza vaccine.…”

Section: Discussionmentioning

confidence: 99%

An intranasal recombinant NDV-BRSV Fopt vaccine is safe and reduces lesion severity in a colostrum-deprived calf model of RSV infection

Sacco

Mena

Palmer

et al. 2022

Sci Rep

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Human respiratory syncytial virus (HRSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, yet no safe, effective vaccine is commercially available. Closely related bovine RSV (BRSV) causes respiratory disease in young calves, with many similar features to those seen in HRSV. We previously showed that a Newcastle disease virus (NDV)-vectored vaccine expressing the F glycoprotein of HRSV reduced viral loads in lungs of mice and cotton rats and protected from HRSV. However, clinical signs and pathogenesis of disease in laboratory animals following HRSV infection differs from that observed in human infants. Thus, we examined whether a similar vaccine would protect neonatal calves from BRSV infection. Codon-optimized rNDV vaccine (rNDV-BRSV Fopt) was constructed and administered to colostrum-deprived calves. The rNDV-BRSV Fopt vaccine was well-tolerated and there was no evidence of vaccine-enhanced disease in the upper airways or lungs of these calves compared to the non-vaccinated calves. We found two intranasal doses reduces severity of gross and microscopic lesions and decreases viral load in the lungs. Furthermore, serum neutralizing antibodies were generated in vaccinated calves. Finally, reduced lung CXC chemokine levels were observed in vaccinated calves after BRSV challenge. In summary, we have shown that rNDV-BRSV Fopt vaccine is safe in colostrum-deprived calves, and is effective in reducing lung lesions, and decreasing viral load in upper respiratory tract and lungs after challenge.

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Potentiating Lung Mucosal Immunity Through Intranasal Vaccination

Cited by 10 publications

References 102 publications

A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination

A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination

1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines

An intranasal recombinant NDV-BRSV Fopt vaccine is safe and reduces lesion severity in a colostrum-deprived calf model of RSV infection

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