Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2

Cao, Huibi; Mai, Juntao; Zhou, Zhichang Peter; Li, Zhijie; Duan, Rongqi; Watt, Jacqueline; Chen, Ziyan; Bandara, Ranmal Avinash; Li, Ming; Ahn, Sang Kyun; Poon, Betty; Christie-Holmes, Natasha; Gray-Owen, Scott D.; Banerjee, Arinjay; Mossman, Karen; Kozak, Rob; Mubareka, Samira; Rini, James M.; Liu, Jun

doi:10.1186/s13578-021-00723-0

Cited by 16 publications

(16 citation statements)

References 64 publications

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“…On the other hand, some animals exhibited CMI response in spleen against RBD. Taking together, we consider that the combination of N+ODN-39M constitutes a promising nasal vaccine component that can be added to the list of enhancers of RBD immune response by this route (Cao et al, 2021), (Du et al, 2021), (Jearanaiwitayakul et al, 2021), (Lazo et al, 2022), (Schild, 2021).…”

Section: Discussionmentioning

confidence: 99%

The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

Lobaina

Chen²,

Suzarte

et al. 2022

Preprint

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Despite the rapid development of vaccines and their reported efficacy for controlling the COVID-19 waves, two key challenges remain: the scope of the immunity against upcoming variants and zoonosis events, and the induction of mucosal immunity able to clear the virus in the upper respiratory tract for halting the transmission. The present study is aiming at assessing a potential component for a new generation of vaccines so as to overcome such limitations. The recombinant nucleocapsid (N) protein from SARS-CoV-2 Delta variant was combined with a phosphodiester backbone CpG ODN (ODN-39M), forming high molecular weight aggregates. The evaluation of its immunogenicity in Balb/C mice revealed that only administration by intranasal route induced a systemic cross-reactive Cell-Mediated-Immunity (CMI). In turn, this combination was able to induce anti-N IgA in lungs, which along with the specific IgG in sera and CMI in spleen, resulted cross-reactive against the nucleocapsid protein of SARS-CoV-1. Furthermore, the nasal administration of the N+ODN-39M preparation combined with the RBD Delta protein, as inductor of neutralizing Abs, enhanced the local and systemic immune response against RBD with a modulation toward a Th1 pattern. Taken together, these results make the N+ODN-39M preparation a suitable component for a future intranasal pancorona vaccine against Sarbecoviruses. Particularly, the bivalent vaccine formulation N+ODN-39M+RBD could be used as an effective nasal booster in previously vaccinated population.

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Section: Discussionmentioning

confidence: 99%

The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

Lobaina

Chen²,

Suzarte

et al. 2022

Preprint

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“…A recent promising approach described results from the use of a helper-dependent adenovirus vector producing secreted, soluble RBD (HD-Ad RBD) for the intranasal immunization of mice [ 90 ]. The HD-Ad RBD vaccine in a prime boost regimen elicited strong mucosal antibody responses in the LRT (IgG and IgA anti-RBD antibodies in bronchiolar lavage fluid), systemic immune responses (neutralizing serum IgG and IgA antibodies, IFNγ producing CD4+ T H cells) and almost completely protected against lung inflammation in transgenic mice expressing human ACE2 on challenge with SARS-CoV-2 [ 90 ]. Importantly, the vaccinated transgenic mice expressing human ACE2 almost completely lacked a replicating virus in oropharyngeal swabs after challenge with SARS-CoV-2, also indicating effective protection in the URT.…”

Section: Urt Immunity After Intranasal Covid-19 Vaccinationmentioning

confidence: 99%

“…Importantly, the vaccinated transgenic mice expressing human ACE2 almost completely lacked a replicating virus in oropharyngeal swabs after challenge with SARS-CoV-2, also indicating effective protection in the URT. The HD-Ad RBD vaccine only produced transient inflammation upon immunization [ 90 ]. It has the advantage of being able to accommodate large gene inserts in the vector, so that multiple RBDs from SARS-CoV-2 variants of concern can be expressed.…”

Section: Urt Immunity After Intranasal Covid-19 Vaccinationmentioning

confidence: 99%

Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

Ramasamy

2022

Viruses

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Increasing evidence shows the nasal epithelium to be the initial site of SARS-CoV-2 infection, and that early and effective immune responses in the upper respiratory tract (URT) limit and eliminate the infection in the URT, thereby preventing infection of the lower respiratory tract and the development of severe COVID-19. SARS-CoV-2 interferes with innate immunity signaling and evolves mutants that can reduce antibody-mediated immunity in the URT. Recent genetic and immunological advances in understanding innate immunity to SARS-CoV-2 in the URT, and the ability of prior infections as well as currently available injectable and potential intranasal COVID-19 vaccines to generate anamnestic adaptive immunity in the URT, are reviewed. It is suggested that the more detailed investigation of URT immune responses to all types of COVID-19 vaccines, and the development of safe and effective COVID-19 vaccines for intranasal administration, are important needs.

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“…Numerous intranasal vaccines utilizing a variety of platforms have been characterized in preclinical K18-hACE2 mouse challenge experiments [14,16,[54][55][56][57][58][46][47][48][49][50][51][52][53]. Intranasal vaccines are also being developed by other labs to improve COVID-19 vaccines, although none reported so far have utilized the virus-like particle, and none have been evaluated preclinically against the highly virulent and pathogenic Delta variant.…”

Section: Discussionmentioning

confidence: 99%

Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice

Damron

Lee

Rader

et al. 2023

Preprint

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As the COVID-19 pandemic transitions to endemic, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD-specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activity in vitro than mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS-CoV-2.

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Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2

Cited by 16 publications

References 64 publications

The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice

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