ORCID Profile
0000-0002-7892-6802
Current Organisation
University of Washington
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Publisher: Elsevier BV
Date: 2019
Publisher: American Society for Clinical Investigation
Date: 11-01-2021
Publisher: Frontiers Media SA
Date: 18-08-2020
Publisher: Elsevier BV
Date: 03-2023
Publisher: Cold Spring Harbor Laboratory
Date: 29-08-2020
DOI: 10.1101/2020.08.27.270975
Abstract: Characterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally s led for correlates of vaccine efficacy. However, patterns of vaccine antigen drainage via the lymphatics after intramuscular immunisation can be stochastic, driving uneven deposition between lymphoid sites, and between in idual lymph nodes within larger clusters. In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. This approach improves the assessment of vaccine-induced immunity in highly relevant non-human primate models.
Publisher: The American Association of Immunologists
Date: 15-07-2021
Abstract: Characterization of germinal center B and T cell responses yields critical insights into vaccine immunogenicity. Nonhuman primates are a key preclinical animal model for human vaccine development, allowing both lymph node (LN) and circulating immune responses to be longitudinally s led for correlates of vaccine efficacy. However, patterns of vaccine Ag drainage via the lymphatics after i.m. immunization can be stochastic, driving uneven deposition between lymphoid sites and between in idual LN within larger clusters. To improve the accurate isolation of Ag-exposed LN during biopsies and necropsies, we developed and validated a method for coformulating candidate vaccines with tattoo ink in both mice and pigtail macaques. This method allowed for direct visual identification of vaccine-draining LN and evaluation of relevant Ag-specific B and T cell responses by flow cytometry. This approach is a significant advancement in improving the assessment of vaccine-induced immunity in highly relevant nonhuman primate models.
Publisher: Cold Spring Harbor Laboratory
Date: 02-09-2020
DOI: 10.1101/2020.09.01.278630
Abstract: SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assessed prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD was associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augmented neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines were comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
Publisher: Springer Science and Business Media LLC
Date: 03-03-2021
DOI: 10.1038/S41467-021-21665-8
Abstract: SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
No related grants have been discovered for Isaac Barber-Axthelm.