Complete protection by a single-dose skin patch–delivered SARS-CoV-2 spike vaccine

McMillan, Christopher L. D.; Choo, Jovin J. Y.; Idris, Adi; Supramaniam, Aroon; Modhiran, Naphak; Amarilla, Alberto A.; Isaacs, Ariel; Cheung, Stacey T. M.; Liang, Bojian; Bielefeldt‐Ohmann, Helle; Azuar, Armira; Acharya, Dev Raj; Kelly, Gabrielle; Fernando, Germain J. P.; Landsberg, Michael J.; Khromykh, Alexander A.; Watterson, Daniel; Young, Paul R.; McMillan, Nigel A.J.; Muller, David A.

doi:10.1126/sciadv.abj8065

Cited by 34 publications

(49 citation statements)

References 76 publications

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“…Our data also demonstrate that a single-dose vaccination of mice with WIV-loaded dMNAs evoked humoral and cellular immune responses and provided protection from influenza infection by reducing viral load in the lungs and disease symptoms. Although prime-boost vaccination regimes are often used to protect from influenza infection 43 , single-dose protection from viral infection in mice after intradermal immunization was also corroborated by other studies using high-density microarray patches containing SARS-CoV-2 spike protein 44 or single intradermal injection with live attenuated influenza vaccine 45 . However, in contrast to these studies, the current study showed only partial protection of mice from influenza infection after single-dose immunization, for both dMNA and intramuscular immunization.…”

Section: Discussionmentioning

confidence: 69%

Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

Tian

Lee

Maaden

et al. 2022

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 69%

Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

Tian

Lee

Maaden

et al. 2022

Journal of Pharmaceutical Sciences

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“…Serum samples were tested for anti-SARS-CoV-2 RBD specific total antibodies by indirect enzyme-linked immunosorbent assay (ELISA) adapted from [ 13 , 14 ]. The receptor-binding domain (RBD) of the spike protein was expressed in ExpiCHO cells and purified as previously described.…”

Section: Methodsmentioning

confidence: 99%

Absence of Anti-RBD Antibodies in SARS-CoV-2 Infected or Naive Individuals Prior to Vaccination with CoronaVac Leads to Short Protection of Only Four Months Duration

et al. 2022

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The COVID-19 pandemic is the biggest public health threat facing the world today. Multiple vaccines have been approved; however, the emergence of viral variants such as the recent Omicron raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac, Beijing, China) vaccine was used; however, it is important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had a history of infection by SARS-CoV-2 prior to immunization, while others did not. We analyzed RBD-specific and neutralizing-antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45–90 days post infection or vaccination, followed by a steady decline over time. In those with a previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection, followed by immunization, resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.

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“…This so-called HexaPro spike glycoprotein expresses as a metastable recombinant SARS-CoV-2 prefusion ectodomain. Extensive comparisons between the native, 2P and HexaPro spike glycoproteins demonstrate that they have comparable native-like protein architecture, have similar antigenic properties including the induction of neutralizing antibodies (20)(21)(22) and have similar glycosylation profiles (18,19,23,24).…”

Section: Antigens Used In This Studymentioning

confidence: 99%

SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation

et al. 2022

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Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted.

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Complete protection by a single-dose skin patch–delivered SARS-CoV-2 spike vaccine

Abstract: Delivery of a SARS-CoV-2 vaccine to the skin of mice via microarray patches provides complete protection from challenge.

Cited by 34 publications

References 76 publications

Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

Absence of Anti-RBD Antibodies in SARS-CoV-2 Infected or Naive Individuals Prior to Vaccination with CoronaVac Leads to Short Protection of Only Four Months Duration

SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation

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