Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques
Katherine McMahanFrank WegmannMalika AïdMichaela SciaccaJinyan LiuNicole P. HachmannJessica MillerCatherine Jacob-DolanOlivia PowersDavid HopeCindy WuJuliana PereiraTetyana MurdzaCamille R. MazurekAmelia HoytAdrianus C. M. BoonMeredith E. Davis-GardnerMehul S. SutharAmanda J. MartinotMona BoursiquotAnthony CookLaurent PessaintMark G. LewisHanné AndersenJeroen TolboomJan SerroyenLaura SolforosiL M M CostesRoland ZahnDan H. Barouch
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Abstract A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants 1,2 , 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 inconsistent 3–7 , 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.Mometasone furoate
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Intranasal microspheres have gained increased interest in recent years.The mucoadhesive properties between microspheres and nasal mucosa via intranasal administration were remarkable affected by factors such as species of polymer materials,molecular weight,pH and modifications.During the process of the preperartion,the mucoadhesion of microspheres has a great relationship between the above facrors.Thus this review focuses on how the above factors affecting the mucoadhesion of microspheres via intranasal administration.
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The theory of intranasal brain-targeting system and its preparations were sumarized to provide basis for traditional Chinese mediline(TCM).literatures searching were based on Keywords as intranasal administration,nasal administration and brain-targeting system.The paper not only described the nasal cavity physiological characteristics to study the transport mechanisms of intranasal drug delivery for brain targeting,but also reviewed the situation of the central nerve system disease treatment using the intranasal drug delivery for brain targeting.The paper also described the new intranasal formulation(in situ gel,liposomes,microspheres,nanoparticles formulations)and traditional Chinese medicine nasal administration to understand the process of traditional Chinese medicine nasal administration.Intranasal brain-targeting preparations of TCM had broad development prospect.
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Intranasal drug administration is a less invasive method of drug delivery that is easily accessible for adult and pediatric patients. Medications administered by the intranasal route have efficacy comparable to intravenous administration and typically have superior efficacy to subcutaneous or intramuscular routes. The intranasal route is beneficial in emergent situations when the intravenous route is not available. The intranasal route is safe and effective in various indications, and therapeutic systemic concentrations of medication can be attained via this route. As the evidence for and comfort with intranasal administration continue to grow, guidance on correct technique, medications, and dosing is vital for appropriate use. This article reviews the process and practices of appropriate intranasal medication administration.
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Objective To explore the feasibility of brain-targeting intranasal administration with β-asarone microemulsion by nose-brain pathway. Methods The concentration of β-asarone in plasma and brain following nasal administration of β-asarone microemulsion(0.42 mL/kg) was measured by HPLC, taking the iv administration of self microemulsion injection as control. And the brain-targeting was evaluated by ratio of AUCbrain/AUCplasma. Results The ratio of AUCbrain/AUCplasma obtained after intranasal administration was significantly higher than that after iv administration. Conclusion The brain-targeting of β-asarone is better after intranasal administration which could become a new drug delivery system for the treatment of Alzheimer's disease.
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It has been shown that stimulated TSH and prolactin levels in intranasal administration of rifathyroin are comparable with the results of i.v. administration of the drug. Intranasal administration can be used for both therapeutic and diagnostic purposes.
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