Intranasal delivery of a chimpanzee adenovirus vector expressing a pre-fusion spike (BV-AdCoV-1) protects golden Syrian hamsters against SARS-CoV-2 infection

Wang, Shen; Xu, Liang; Mu, Ting; Qin, Mian; Zhao, Ping; Xie, Lei; Du, Lidong; Wu, Yue; Legrand, Nicolas; Mouchain, Karine; Fichet, Guillaume; Liu, Yi; Wang, Yin; Zhao, Jin; Ji, Min; Gong, Bin; Klein, Michel; Wu, Ke

doi:10.3389/fcimb.2022.979641

Cited by 5 publications

(7 citation statements)

References 36 publications

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“…Strikingly, neutralization titers against BA.2 were non-existent after a single dose in hamsters and only detectable in four out of 20 animals after a booster dose. This contrasts both adenovirus and modified vaccinia Ankara (MVA) vaccines encoding the Wuhan spike in its wildtype or prefusion conformation (two proline substitution) where robust cross-reactive serum neutralizing antibodies are observed [62][63][64][65][66][67] . Induced antibodies exhibited varied binding abilities to different VOCs, as observed with the antibodies resultant of NDV-PFS vaccination 62,63,66,67 .…”

Section: Discussionmentioning

confidence: 94%

Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges

Warner,

Yates,

Vendramelli

et al. 2024

npj Vaccines

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The rapid development and deployment of vaccines following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions of lives. Despite their immense success, there remains a need for next-generation vaccination approaches for SARS-CoV-2 and future emerging coronaviruses and other respiratory viruses. Here we utilized a Newcastle Disease virus (NDV) vectored vaccine expressing the ancestral SARS-CoV-2 spike protein in a pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters and K18 mice against Delta and Omicron SARS-CoV-2 variants of concern. Additionally, intranasal vaccination induced robust, durable protection that was extended to 6 months post-vaccination. Overall, our data provide evidence that NDV-vectored vaccines represent a viable next-generation mucosal vaccination approach.

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Section: Discussionmentioning

confidence: 94%

Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges

Warner,

Yates,

Vendramelli

et al. 2024

npj Vaccines

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“…We previously reported that the intranasal administration of BV-AdCoV-1 induced strong humoral and cellular protective immunity in golden hamsters [ 25 ]. We turned to the non–human primate model to further compare the respective efficiencies of intranasal administration (IN) and aerosol inhalation (IH).…”

Section: Resultsmentioning

confidence: 99%

“…The prime–boost schedules of COVID-19 vaccines have unambiguously demonstrated their safety, clinical effectiveness, and efficacy [ 25 ]. However, recent reports have consistently highlighted that immunity begins to decline 6–8 months after two vaccine doses [ 1 ], exposing vaccinees to re–infection or breakthrough infections, in particular by emerging SARS-CoV-2 variants.…”

Section: Discussionmentioning

confidence: 99%

“…The BV-AdCoV-1 vector expressing the ancestral Wuhan Hu–1 prefusion spike gene was constructed as previously described [ 25 ] and shown to protect golden Syrian hamsters against SARS-CoV-2 infection without disease enhancement post–challenge. The particle size distribution of aerosols generated by nebulizing BV-AdCoV-1 was determined using a Winner 311XP laser light scattering particle analyzer (Jinan, China).…”

Section: Methodsmentioning

confidence: 99%

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Aerosol Inhalation of Chimpanzee Adenovirus Vectors (ChAd68) Expressing Ancestral or Omicron BA.1 Stabilized Pre–Fusion Spike Glycoproteins Protects Non–Human Primates against SARS-CoV-2 Infection

Wang,

Qin,

et al. 2023

Vaccines

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Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication–deficient adenovirus–vectored COVID-19 vaccine expressing a stabilized pre–fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan–Hu–1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus–based Omicron BA.1 vaccine (C68–COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68–COA04 vector resulted in cross–neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68–COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68–COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread.

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“…However, the main route of infection by SARS-CoV-2 is through the upper respiratory tract, and a vaccine with a protective effect at the site of infection is desired. In contrast to intramuscular vaccination, mucosal immunization is a non-invasive procedure that induces a strong and long-lasting secretory immunoglobulin A (IgA) response and plays an important role in defense against viral infection of the upper respiratory tract (1)(2)(3). Therefore, it is important to study mucosal immunity, especially nasal immunity, which has been shown to play an important role in IgA production, mainly in nasal-associated lymphoid tissue (NALT) and Waldeyer's tonsillar ring (4)(5)(6), which appears to be functionally equivalent to NALT in rodents (7).…”

Section: Introductionmentioning

confidence: 99%

Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination

et al. 2023

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Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3–6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3–6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3–6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3–6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3–6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.

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Intranasal delivery of a chimpanzee adenovirus vector expressing a pre-fusion spike (BV-AdCoV-1) protects golden Syrian hamsters against SARS-CoV-2 infection

Cited by 5 publications

References 36 publications

Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges

Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges

Aerosol Inhalation of Chimpanzee Adenovirus Vectors (ChAd68) Expressing Ancestral or Omicron BA.1 Stabilized Pre–Fusion Spike Glycoproteins Protects Non–Human Primates against SARS-CoV-2 Infection

Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination

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