Biology subjects

Swanson, W.

Publications and source records attributed to Swanson, W..

5 recordsLinked to original sources

bioRxiv2025

Preclinical immunogenicity of the LP.8.1-adapted BNT162b2 COVID-19 vaccine

SARS-CoV-2 evolution toward antigenically distinct lineages drives escape from host immunity. JN.1 lineage derivatives have recently dominated the global epidemiologic landscape. In preclinical models, an LP.8.1-adapted BNT162b2 vaccine elicited higher serum neutralizing antibody responses against contemporary, circulating JN.1 sublineages, including the currently dominant XFG, as compared to JN.1-, KP.2- and XEC-adapted vaccines. These findings supported the selection of an LP.8.1-adapted vaccine for the composition of the 2025-26 COVID-19 vaccine formula.

immunology↗

bioRxiv2024

Immunologic and Biophysical Features of the BNT162b2 JN.1- and KP.2-Adapted COVID-19 Vaccines

Vaccines remain a vital public health tool to reduce the burden of COVID-19. COVID-19 vaccines that are more closely matched to circulating SARS-CoV-2 lineages elicit more potent and relevant immune responses that translate to improved real-world vaccine effectiveness. The rise in prevalence of the Omicron JN.1 lineage, and subsequent derivative sublineages such as KP.2 and KP.3, coincided with reduced neutralizing activity and effectiveness of Omicron XBB.1.5-adapted vaccines. Here, we characterized the biophysical and immunologic attributes of BNT162b2 JN.1- and KP.2-adapted mRNA vaccine-encoded spike (S) protein immunogens. Biophysical interrogations of S revealed the structural consequences of hallmark amino acid substitutions and a potential molecular mechanism of immune escape employed by JN.1 and KP.2. The vaccine candidates were evaluated for their immunogenicity when administered as fourth or fifth doses in BNT162b2-experienced mice or as a primary series in naive mice. In both vaccine-experienced and naive settings, JN.1- and KP.2-adapted vaccines conferred improved neutralizing responses over the BNT162b2 XBB.1.5 vaccine against a broad panel of emerging JN.1 sublineages, including the predominant KP.3.1.1 and emerging XEC lineages. Antigenic mapping of neutralizing responses indicated greater antigenic overlap of JN.1- and KP.2-adapted vaccine responses with currently circulating sublineages compared to an XBB.1.5-adapted vaccine. CD4+ and CD8+ T cell responses were generally conserved across all three vaccines. Together, the data support the selection of JN.1- or KP.2-adapted vaccines for the 2024-25 COVID-19 vaccine formula. ONE-SENTENCE SUMMARYThe Omicron JN.1- and KP.2-adapted BNT162b2 mRNA vaccines encoding prefusion S proteins elicit similar preclinical neutralizing antibody responses against circulating JN.1 sublineage pseudoviruses that are more potent than those elicited by past iterations of BNT162b2 licensed vaccines, thus demonstrating the importance of annual strain changes to the COVID-19 vaccine.

immunology↗

bioRxiv2020

Zika virus-based immunotherapy enhances long-term survival of rodents with brain tumors through upregulation of memory T-cells

Zika virus (ZIKV) exhibits a tropism for brain tumor cells and has been used as an oncolytic virus to target brain tumors in mice with modest effects on extending median survival. Recent studies have highlighted the potential for combining virotherapy and immunotherapy to target cancer. We postulated that ZIKV could be used as an adjuvant to enhance the long-term survival of mice with malignant glioblastoma and generate memory T-cells capable of providing long-term immunity against cancer remission. To test this hypothesis mice bearing malignant intracranial GL261 tumors were subcutaneously vaccinated with irradiated GL261 cells previously infected with the ZIKV. Mice also received intracranial injections of live ZIKV, irradiated ZIKV, or irradiated GL261 cells previously infected with ZIKV. Long-term survivors were rechallenged with a second intracranial tumor to examine their immune response and look for the establishment of protective memory T-cells. Mice with subcutaneous vaccination plus intracranial irradiated ZIKV or intracranial irradiated GL261 cells previously infected with ZIKV exhibited the greatest extensions to overall survival. Flow cytometry analysis of immune cells within the brains of long-term surviving mice after tumor rechallenge revealed an upregulation in the levels of T-cells, including CD4+ and tissue-resident memory CD4+ T-cells, in comparison to long-term survivors that were mock-rechallenged, and in comparison to naive untreated mice challenged with intracranial gliomas. These results suggest that ZIKV can serve as an adjuvant to subcutaneous tumor vaccines that enhance long-term survival and generate protective tissue-resident memory CD4+ T-cells.

cancer biology↗

bioRxiv2020

Proteomics support the threespine stickleback egg coat as a protective oocyte envelope

After the end of the last ice age, ancestrally marine threespine stickleback fish (Gasterosteus aculeatus) have undergone an adaptive radiation into freshwater environments throughout the Northern Hemisphere, creating an excellent model system for studying molecular adaptation and speciation. Stickleback populations are reproductively isolated to varying degrees, despite the fact that they can be crossed in the lab to produce viable offspring. Ecological and behavioral factors have been suggested to underlie incipient stickleback speciation. However, reproductive proteins represent a previously unexplored driver of speciation. As mediators of gamete recognition during fertilization, reproductive proteins both create and maintain species boundaries. Gamete recognition proteins are also frequently found to be rapidly evolving, and their divergence may culminate in reproductive isolation and ultimately speciation. As an initial investigation into the contribution of reproductive proteins to stickleback reproductive isolation, we characterized the egg coat proteome of threespine stickleback eggs. In agreement with other teleosts, we find that stickleback egg coats are comprised of homologs to the zona pellucida (ZP) proteins ZP1 and ZP3. We explore aspects of stickleback ZP protein biology, including glycosylation, disulfide bonding, and sites of synthesis, and find many substantial differences compared to their mammalian homologs. Furthermore, molecular evolutionary analyses indicate that ZP3, but not ZP1, has experienced positive Darwinian selection across teleost fish. Taken together, these changes to stickleback ZP protein architecture suggest that the egg coats of stickleback fish, and perhaps fish more generally, have evolved to fulfill a more protective functional role than their mammalian counterparts. Data are available via ProteomeXchange with identifiers PXD017488 and PXD017489.

molecular biology↗

bioRxiv2017

Unbiased Definition Of A Shared T-Cell Receptor Motif Enables Population-Based Studies Of Tuberculosis

Peptide-specific T cells that are restricted by highly polymorphic major histocompatibility complex (MHC) proteins express diverse T-cell receptors (TCRs) that are rarely shared among unrelated individuals. T-cells can also recognize bacterial lipid antigens that bind the relatively non-polymorphic CD1 family of proteins. However, genetic variation in human CD1 genes and TCR diversity expressed by CD1-restricted T-cells have not been quantitatively determined. Here, we show that CD1B is nearly nucleotide-identical across all five continental ancestry groups, providing evidence for purifying selection during human evolution. We used CD1B tetramers loaded with a mycobacterial glycolipid antigen to isolate T-cells from four genetically unrelated South African adults and cataloged thousands of TCRs from in-vitro expanded T-cells using immunosequencing. We identified highly conserved motifs that were co-expressed as a functional heterodimer and significantly enriched among tetramer-positive T-cells sorted directly from peripheral blood. Finally, we show that frequencies of these TCR motifs are increased in the blood of patients with active tuberculosis compared to uninfected controls, a finding that is confirmed by ex-vivo frequencies of tetramer-positive T-cells determined by flow cytometry. These data provide a framework for unbiased definition of TCRs targeting lipid antigens, which can be tested for clinical associations independently of host genetic background.\n\nBrief SummaryWe used human genetics and immunosequencing to define a shared T-cell receptor motif that is specific for a mycobacterial lipid antigen and associated with tuberculosis independently of host genetic background.

immunology↗