Skin-patch delivered subunit vaccine induces broadly neutralising antibodies against SARS-CoV-2 variants of concern

McMillan, Christopher L. D.; Amarilla, Alberto A.; Modhiran, Naphak; Choo, Jovin J. Y.; Azuar, Armira; Honeyman, Kate; Khromykh, Alexander A.; Young, Paul R.; Watterson, Daniel; Muller, David A.

doi:10.1016/j.vaccine.2022.07.013

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…Standard ELISAs were undertaken using SARS-CoV-2 recombinant spike proteins from each variant of concern as antigens. These recombinant spike proteins were stabilized via six proline substitutions and mutated furin cleavage sites, and were expressed in Expi293-F™ cells [ 29 , 45 ]. The N-terminal domain (NTD) of the spike protein from the original strain was also used as an antigen [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Morgan

Yan

et al. 2022

Viruses

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The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spawned an ongoing demand for new research reagents and interventions. Herein we describe a panel of monoclonal antibodies raised against SARS-CoV-2. One antibody showed excellent utility for immunohistochemistry, clearly staining infected cells in formalin-fixed and paraffin embedded lungs and brains of mice infected with the original and the omicron variants of SARS-CoV-2. We demonstrate the reactivity to multiple variants of concern using ELISAs and describe the use of the antibodies in indirect immunofluorescence assays, Western blots, and rapid antigen tests. Finally, we illustrate the ability of two antibodies to reduce significantly viral tissue titers in K18-hACE2 transgenic mice infected with the original and an omicron isolate of SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Morgan

Yan

et al. 2022

Viruses

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“…These data are consistent with the reported vaccines, such as those based on mRNAs, viral vectors, and inactivated viruses, which showed reduced neutralizing activity against the Omicron or its subvariants as compared to the original virus isolate or other VOCs 28 – 31 . Similarly, skin-patch delivery of a HexaPro S protein of the original SARS-CoV-2 strain elicited higher neutralizing antibody titers against the Gamma and Delta VOCs and original strain, but relatively lower titers of neutralizing antibodies against the Omicron VOC 32 . Previously reported vaccines demonstrated folded reduction of neutralizing antibodies against the Omicron BA4 and BA5 subvariants than against the BA1, BA2, or BA2.12.1 subvariant 28 , 31 , 33 .…”

Section: Discussionmentioning

confidence: 98%

Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern

et al. 2022

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The SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective vaccines to prevent multiple SARS-CoV-2 VOCs. Here, we evaluated the neutralizing activity and protection conferred by a BA1-S subunit vaccine when combined with or used as booster doses after, administration of wild-type S protein (WT-S). A WT-S/BA1-S cocktail, or WT-S prime and BA1-S boost, induced significantly higher neutralizing antibodies against pseudotyped Omicron BA1, BA2, BA2.12.1, and BA5 subvariants, and similar or higher neutralizing antibodies against the original SARS-CoV-2, than the WT-S protein alone. The WT-S/BA1-S cocktail also elicited higher or significantly higher neutralizing antibodies than the WT-S-prime-BA1-S boost, WT-S alone, or BA1-S alone against pseudotyped SARS-CoV-2 Alpha, Beta, Gamma, and Delta VOCs, and SARS-CoV, a closely related beta-coronavirus using the same receptor as SARS-CoV-2 for viral entry. By contrast, WT-S or BA1-S alone failed to induce potent neutralizing antibodies against all these viruses. Similar to the WT-S-prime-BA1-S boost, the WT-S/BA1-S cocktail completely protected mice against the lethal challenge of a Delta variant with negligible weight loss. Thus, we have identified an effective vaccination strategy that elicits potent, broadly, and durable neutralizing antibodies against circulating SARS-CoV-2 Omicron subvariants, other VOCs, original SARS-CoV-2, and SARS-CoV. These results will provide useful guidance for developing efficacious vaccines that inhibit current and future SARS-CoV-2 variants to control the COVID-19 pandemic.

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“…Additionally, the HD-MAP does not generate sharps waste and offers advantages in ease of use relative to needle-and-syringe injection, both beneficial traits in the context of mass vaccination campaigns where highly trained healthcare workers may be otherwise occupied. We have previously demonstrated that delivery of a stabilised SARS-CoV-2 spike protein called HexaPro [7] via the HD-MAP increased serum antibodies with neutralization capacity against SARS-CoV-2 and associated variants compared to intradermal injection, and elicited protection following only a single dose in a mouse model of infection [1,8,9]. In the previous studies, only limited analysis of the cellular immune responses generated by HD-MAP vaccination was performed, where enhanced interferon (IFN)-γ secreting cells were observed via enzyme-linked immunospot (ELISpot) [1].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of cellular immunity following needle-free vaccination of mice with SARS-CoV-2 spike protein

McMillan,

Wijesundara,

Choo

et al. 2024

Journal of General Virology

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The COVID-19 pandemic has highlighted the need for vaccines capable of providing rapid and robust protection. One way to improve vaccine efficacy is delivery via microarray patches, such as the Vaxxas high-density microarray patch (HD-MAP). We have previously demonstrated that delivery of a SARS-CoV-2 protein vaccine candidate, HexaPro, via the HD-MAP induces potent humoral immune responses. Here, we investigate the cellular responses induced by HexaPro HD-MAP vaccination. We found that delivery via the HD-MAP induces a type one biassed cellular response of much greater magnitude as compared to standard intramuscular immunization.

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Skin-patch delivered subunit vaccine induces broadly neutralising antibodies against SARS-CoV-2 variants of concern

Cited by 8 publications

References 20 publications

Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern

Enhancement of cellular immunity following needle-free vaccination of mice with SARS-CoV-2 spike protein

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