Single-Dose Intranasal Vaccination Elicits Systemic and Mucosal Immunity Against SARS-CoV-2

An, Xingyue; Martínez-Paniagua, Melisa; Rezvan, Ali; Sefat, Samiur Rahman; Fathi, Mohsen; Singh, Shailbala; Biswas, Sujit; Pourpak, Melissa; Yee, Cassian; Liu, Xinli; Varadarajan, Navin

doi:10.2139/ssrn.3751056

Cited by 16 publications

(21 citation statements)

References 33 publications

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“…More recently, it has been shown that a subunit vaccine of SC2 S protein, along with a liposomal STING agonist as an adjuvant, can induce a strong mucosal immunity upon IN delivery in a mouse model. 21 However, a subunit vaccine may not elicit neutralizing antibodies sufficient to cover protection against the wide range of variants currently spreading across the globe. Hence, we evaluated our IN-DNA vaccine against SC2 S protein, and this strategy can, in theory, be extended to mRNA vaccines coding for different SC2 structural proteins (S, N, E, and M) to elicit immunity that can protect from all different variants in all viral proteins.…”

Section: Resultsmentioning

confidence: 99%

Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle

et al. 2021

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The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2 (SC2). A variety of anti-SC2 vaccines have been approved for human applications, including those using messenger RNA (mRNA), adenoviruses expressing SC2 spike (S) protein, and inactivated virus. The protective periods of immunization afforded by these intramuscularly administered vaccines are currently unknown. An alternative self-administrable vaccine capable of mounting long-lasting immunity via sterilizing neutralizing antibodies would be hugely advantageous in tackling emerging mutant SC2 variants. This could also diminish the possibility of vaccinated individuals acting as passive carriers of COVID-19. Here, we investigate the potential of an intranasal (IN)-delivered DNA vaccine encoding the S protein of SC2 in BALB/c and C57BL/6J immunocompetent mouse models. The immune response to IN delivery of this SC2-spike DNA vaccine transported on a modified gold-chitosan nanocarrier shows a strong and consistent surge in antibodies (IgG, IgA, and IgM) and effective neutralization of pseudoviruses expressing S proteins of different SC2 variants (Wuhan, beta, and D614G). Immunophenotyping and histological analyses reveal chronological events involved in the recognition of SC2 S antigen by resident dendritic cells and alveolar macrophages, which prime the draining lymph nodes and spleen for peak SC2-specific cellular and humoral immune responses. The attainable high levels of anti-SC2 IgA in lung mucosa and tissue-resident memory T cells can efficiently inhibit SC2 and its variants at the site of entry and also provide long-lasting immunity.

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Section: Resultsmentioning

confidence: 99%

Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle

et al. 2021

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“…An IN alum adjuvanted RBD based vaccine demonstrated induction of neutralizing antibody responses in mice, however no significant T-cell response was induced ( 76 ). Another candidate consisting of a STING agonist encapsulated in liposomes has shown promise with SARS-CoV-2 full-length S protein in safely inducing systemic, mucosal, and cellular immunity ( 77 ). While direct quantitative comparisons of this adjuvant with NE/IVT cannot be made due to differences in methodologies (i.e.…”

Section: Discussionmentioning

confidence: 99%

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

et al. 2021

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Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.

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“…Single-cell RNA-sequencing confirmed the activation of T and B cells within the NALT, which is the inductive site to elicit potent and long-lasting immunity locally and systemically. 71 Kim et al. utilized self-assembling Helicobacter pylori-bullfrog ferritin nanoparticles to deliver a RBD protein vaccine of SARS-CoV-2.…”

Section: Recent Progress In the Development Of Intranasal Covid-19 Vaccinesmentioning

confidence: 99%

“… 106 A COVID-19 vaccine successfully incorporated S protein antigen and a commercial agonist of STING, 2′−3′’cyclic guanosine monophosphate adenosine monophosphate (cGAMP), into liposomes for IN immunization. 71 A mixed adjuvant composed of various TLR agonists (CpG (TLR9), LP1569 (TLR2)) and c-di-GMP induced IL-17-secreting T RM cells after IN immunization, which were responsible for sustained protective immunity against Bordetella pertussis nasal colonization. 107 RIG-I can detect endogenous and exogenous RNA to initiate innate antiviral immunity.…”

Section: Adjuvants For Intranasal Vaccinesmentioning

confidence: 99%

Intranasal COVID-19 vaccines: From bench to bed

Alu¹,

Chen²,

et al. 2022

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Currently licensed COVID-19 vaccines are all designed for intramuscular (IM) immunization. However, vaccination today failed to prevent the virus infection through the upper respiratory tract, which is partially due to the absence of mucosal immunity activation. Despite the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the next generation of COVID-19 vaccine is in demand and intranasal (IN) vaccination method has been demonstrated to be potent in inducing both mucosal and systemic immune responses. Presently, although not licensed, various IN vaccines against SARS-CoV-2 are under intensive investigation, with 12 candidates reaching clinical trials at different phases. In this review, we give a detailed description about current status of IN COVID-19 vaccines, including virus-vectored vaccines, recombinant subunit vaccines and live attenuated vaccines. The ongoing clinical trials for IN vaccines are highlighted. Additionally, the underlying mechanisms of mucosal immunity and potential mucosal adjuvants and nasal delivery devices are also summarized.

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Single-Dose Intranasal Vaccination Elicits Systemic and Mucosal Immunity Against SARS-CoV-2

Cited by 16 publications

References 33 publications

Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle

Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

Intranasal COVID-19 vaccines: From bench to bed

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