A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Hassan, Ahmed O.; Kafai, Natasha M.; Dmitriev, Igor; Fox, Julie M.; Smith, Brian K.; Harvey, Ian B.; Chen, Rita E.; Winkler, Emma S.; Wessel, Alex W.; Case, James Brett; Kashentseva, Elena A.; McCune, Broc T.; Bailey, Adam L.; Zhao, Haiyan; VanBlargan, Laura A.; Dai, Ya-Nan; Ma, Mingyu; Adams, Lucas J.; Shrihari, Swathi; Gralinski, Lisa E.; Hou, Yixuan J.; Schaefer, Alexandra; Kim, Arthur S.; Keeler, Shamus P.; Weiskopf, Daniela; Baric, Ralph S.; Holtzman, Michael J.; Fremont, D.H.; Curiel, David T.; Diamond, Michael S.

doi:10.1101/2020.07.16.205088

Cited by 10 publications

(13 citation statements)

References 69 publications

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“…To date, six intranasal and three oral vaccine candidates are in clinical Phase 1 or 2 trials [ 2 ]. While data from clinical trials have not yet been published, preclinical studies suggest the induction of mucosal immunity [ 69 ]. First results from clinical trials of an oral vaccine candidate by Vaxart Inc. have recently been announced [ 70 ].…”

Section: Immune Response To Sars-cov-2 Vaccinesmentioning

confidence: 99%

Correlates of Vaccine-Induced Protection against SARS-CoV-2

et al. 2021

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We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP.

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Section: Immune Response To Sars-cov-2 Vaccinesmentioning

confidence: 99%

Correlates of Vaccine-Induced Protection against SARS-CoV-2

et al. 2021

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“…Whether or not strong immune responses to the S protein alone will provide adequate protection is still unclear, but the limited evidence from the animal challenge studies previously discussed seem to indicate that this may be sufficient to protect against severe disease. More recently, trials deploying intranasal immunisation using the S protein have been shown to elicit a broad spectrum of antibodies and T cell responses, including local mucosal responses, which may be a promising avenue for improving vaccine efficacy ( 163 ).…”

Section: Discussionmentioning

confidence: 99%

“…This route of administration may fail to generate a protective immune response in the upper respiratory tract that would otherwise be generated in natural infection ( 98 ). Hassan et al demonstrated that a single-dose of intranasal administration of a ChAd-vectored S vaccine induced a local immune response that was sufficient to provide sterilising immunity in mice ( 163 ). There is reason to believe that local immunisation with a vaccine that can generate an IgA mucosal antibody response in the upper respiratory tract may provide a robust strategy for effective early clearance, as shown in successful trials of measles and BCG vaccines administered through the aerosol route ( 164 , 165 ).…”

Section: Vaccine-induced Immunitymentioning

confidence: 99%

Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

2020

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In December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China resulted in the current COVID-19 global pandemic. The human immune system has not previously encountered this virus, raising the important question as to whether or not protective immunity is generated by infection. Growing evidence suggests that protective immunity can indeed be acquired post-infection—although a handful of reinfection cases have been reported. However, it is still unknown whether the immune response to SARS-CoV-2 leads to some degree of long-lasting protection against the disease or the infection. This review draws insights from previous knowledge regarding the nature and longevity of immunity to the related virus, SARS-CoV, to fill the gaps in our understanding of the immune response to SARS-CoV-2. Deciphering the immunological characteristics that give rise to protective immunity against SARS-CoV-2 is critical to guiding vaccine development and also predicting the course of the pandemic. Here we discuss the recent evidence that characterises the adaptive immune response against SARS-CoV-2 and its potential implications for the generation of memory responses and long-term protection.

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“…We saw stronger serum IgG and NAb titers in our study compared to a ChAdOx1-nCov in Balb/c mice 4 , however, this might reflect differences in assay components. A rAd36 vaccine study was performed by Hassan, et al, where doses of 1e10 VP were given by intranasal delivery 49 . The results were significant from the standpoint of blocking lung infection in a mouse SARS-CoV-2 challenge model.…”

Section: Discussionmentioning

confidence: 99%

Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection

Moore

Dora

Peinovich

et al. 2020

Preprint

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There is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirus-based vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This full-length spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development.

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A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Cited by 10 publications

References 69 publications

Correlates of Vaccine-Induced Protection against SARS-CoV-2

Correlates of Vaccine-Induced Protection against SARS-CoV-2

Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection

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