Biology subjects

Diamond, M. S.

Publications and source records attributed to Diamond, M. S..

At least 19 recordsLinked to original sources

bioRxiv2026

MXRA8-dependent chikungunya virus infection in PDGFRα+ mesenchymal cells increases vascular permeability and facilitates hematogenous spread

Alphaviruses are mosquito-transmitted pathogens in the Togaviridae family that cause severe arthritogenic or encephalitic disease in humans. Swelling of peripheral joints and soft tissues is a hallmark of arthritogenic alphavirus infection, although the mechanism by which tissue edema occurs is not well understood. The cell surface protein, matrix remodeling-associated protein 8 (MXRA8), is a cell entry receptor for several arthritogenic alphaviruses. Global loss of MXRA8 expression in mice abrogates foot swelling and reduces virus dissemination. Here, we demonstrate that specific ablation of MXRA8 from platelet-derived growth factor receptor alpha (PDGFR) cells, including fibroblasts, phenocopies the foot swelling and dissemination deficits observed in chikungunya virus (CHIKV)-infected global MXRA8 knock-out mice. Edema in the foot requires CHIKV infection of PDGFR+ cells, which enhances both infection efficiency and permeability of endothelial cells. CHIKV-induced vascular leakage requires both MXRA8 expression and vascular endothelial growth factor signaling and contributes to dissemination by enabling virus access to the bloodstream. Collectively, our study establishes the role of MXRA8-dependent cell tropism in CHIKV dissemination and pathogenesis.

microbiology↗

bioRxiv2026

Human iPSC-derived neurons identify West Nile virus neuropathogenesis signatures and reveal strain-dependent neuroattenuation

West Nile virus (WNV) is one of the leading causes of arthropod-transmitted encephalitis in the world, yet its effects on neurons, the principal target of WNV in the brain, remain poorly defined. Here we establish and use Ngn2-induced human iPSC-derived glutamatergic neurons to define the neuronal response to WNV through integrated temporal proteomics and transcriptomics. Temporal multi-omic profiling revealed that infection activated innate immunity and the Unfolded Protein Response while suppressing axonogenesis and synaptic programs. WNV infection also disrupted calcium homeostasis, reduced STMN2 abundance, and promoted cytoplasmic redistribution of TDP-43. Applying this neuronal model to characterize contemporary California isolates, we identified LA24, a lineage 1 strain that replicates efficiently in non-neuronal cell lines but is selectively attenuated in neurons, with reduced viral burden in the brain and attenuated pathogenicity in mice. Together, these findings uncover neuron-specific signatures of WNV pathogenesis and demonstrate that neuronal replication phenotypes can reveal strain-dependent virulence differences not captured by conventional cell lines.

microbiology↗

bioRxiv2026

Small intestinal microbiota of undernourished women perturbs placental development in mice

Children of undernourished women have impaired pre- and postnatal growth. Undernourished women and children have a high incidence of environmental enteric dysfunction (EED), an enteropathy characterized by gut barrier dysfunction and systemic inflammation. Here, we employ gnotobiotic mice to compare the effects of bacterial consortia cultured from the duodenal microbiota of Bangladeshi women with EED and their healthy counterparts. Female mice harboring the EED-derived consortium exhibited fetal and placental growth restriction. Transcriptomic and proteomic analyses disclosed pronounced effects of the EED-derived consortium on the decidual component of the maternal-fetal interface involving tissue-resident uterine natural killer (uNK) cells and disruption of TGF-{beta} signaling between uNK and decidual stromal cells. Co-housing mice with EED and healthy consortia ameliorated these effects, disclosing bacterial targets to improve prenatal development.

systems biology↗

bioRxiv2026

Convergent IGHV3-53/3-66 antibodies elicited by Omicron BA.1 infection broadly neutralize emerging SARS-CoV-2 variants

Natural SARS-CoV-2 infections or vaccinations induce neutralizing antibodies (nAbs) offer protection from severe disease. The shared use of IGHV3-53/3-66 genes makes this class of monoclonal antibodies (mAbs) a public clonotype and is well established, but the evolution and structural basis of how these public antibodies maintain broad binding and acquire potent neutralizing activity is not completely understood. To understand how these features are facilitated by the IGHV3-53/3-66 germline segments and enhanced by somatic mutations, we investigated the biology of a panel of 242 human mAbs isolated from an individual infected with SARS-CoV-2 BA.1 strain and recovered. Interestingly, a mAb designated COV2-3731 encoded by IGHV3-53/IGKV1-33 retained potent neutralizing activity against SARS-CoV-2 variants BA.2.86, JN.1, KP.2, BA.3.2, and, to some extent, KP.3. Studies using deep mutational scanning with a BA.2 lentiviral library and determination of the structural complex of the BA.2 S protein and COV2-3731 Fab fragments using cryo-EM revealed key contact residues. Further, germline revertant analysis of the COV2-3731 mAb provided additional insights into how this COV2-3731 and other IGHV3-53/3-66-encoded public antibodies evolve to gain breadth against antigenically distinct SARS-CoV-2 variants such as BA.2.86, JN.1, KP.2, and BA.3.2.

immunology↗

bioRxiv2026

Antigenic characterization of SARS-CoV-2 variants BA.3.2.1 and BA.3.2.2 in three animal models

BA.3.2, a variant of SARS-CoV-2 containing [~]40 mutations in its spike protein compared to its nearest ancestor, has spread globally since its first detection in South Africa in November 2024. Here, we report antigenic characterization of BA.3.2 viruses in three naive animal models, and visualize its antigenic phenotype in the context of SARS-CoV-2 evolution using antigenic cartography. We find that: (1) BA.3.2 is substantially antigenically divergent from existing SARS-CoV-2 variants; (2) infection with BA.3.2 in hamster and mouse animal models produces sera with lower homologous titer than infection with other variants. Both of these results may have implications for the selection of vaccine antigens.

microbiology↗

bioRxiv2026

CD164 is an endolysosomal host factor for entry of Clade A New World Arenaviruses

Arenaviruses are divided into Old World (OW) and New World (NW) groups. OW arenaviruses enter cells through a pH-dependent receptor switch from a plasma-membrane factor to an endolysosomal receptor for subsequent membrane fusion, whereas clade B NW arenaviruses use transferrin receptor 1 without a secondary receptor. Using a vesicular stomatitis virus (VSV) chimera expressing the glycoprotein complex (GPC) of the clade A NW arenavirus Pichinde virus, we performed a genome-wide CRISPR loss-of-function screen and identified the endolysosomal sialomucin CD164 as an essential host factor. CD164 knockout cells were resistant to VSV chimeras bearing the GPCs of Pichinde, Parana, and Flexal viruses, and to authentic Pichinde and Parana virus, with susceptibility restored by complementation. The requirement mapped to the cysteine-rich domain of CD164, which bound GP1 in a pH-dependent manner through main-chain interactions. These findings define CD164 as an endolysosomal receptor for clade A NW arenaviruses expanding the receptor switching paradigm.

microbiology↗

bioRxiv2026

TMEM106B mediates ACE2-independent replication of the SARS-CoV-2 S-E484D variant in airway-derived cell models

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause significant respiratory disease, particularly in vulnerable populations. Although ACE2 is the primary receptor for viral entry, previous studies have identified a naturally occurring, ACE2-independent entry pathway in certain airway-derived cell lines. Utilization of this pathway depends on surface heparan sulfates and requires the E484D substitution within the receptor-binding domain of the viral Spike (S) protein. In this study, we expand the panel of airway-derived cell lines that support ACE2-independent, S-E484D-dependent replication and identify the host lysosomal transmembrane protein TMEM106B as a critical host factor for infection. Knockout of TMEM106B completely abolishes infection by SARS-CoV-2 SE484D in NCI-H522 and NCI-H661 cells. Moreover, ectopic expression of the luminal C-terminal domain (CTD) of TMEM106B-either alone or redirected to the plasma membrane - is sufficient to enable viral entry and infection in otherwise non-permissive cells. We further show that Fc-TMEM106B-CTD decoy protein blocks infection by SARS-CoV-2 SE484D, supporting a direct interaction between the S-E484D protein and TMEM106B-CTD. Finally, passaging experiments with a chimeric VSV-SARS-CoV-2 SE484D identify additional mutations within the heptad repeat 1 that enhance TMEM106B utilization and viral spread in the ACE2-independent cell models. Together, these findings demonstrate that TMEM106B is a key mediator of a naturally occurring ACE2-independent pathway in multiple airway-derived cells lines and suggest that variation in the Spike protein can expand receptor usage by SARS-CoV-2. IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to acquire mutations in the viral spike (S) protein as it circulates in humans. How these mutations influence the cell and tissue tropism of SARS-CoV-2 remains poorly understood. While ACE2 is the canonical host cell receptor for SARS-CoV-2, previous studies revealed the presence of a naturally occurring ACE2-independent entry pathway in multiple airway-derived cell lines that can be utilized only by a SARS-CoV-2 variant bearing the E484D substitution within the viral S protein. Here we expand the airway-derived cell line models that support ACE2-independent and S-E484D-dependent entry and show that the host lysosomal transmembrane protein, TMEM106B, is an essential viral entry factor. Although the E484D substitution is currently rare in human isolates, our findings raise the possibility that small mutations in SARS-CoV-2 S can allow the utilization of alternative entry pathways that broadens its cell and tissue tropism.

microbiology↗

bioRxiv2025

Gut microbe-derived short-chain fatty acids regulate joint inflammation and activation of infiltrating and resident myeloid cells after alphavirus infection

Although oral antibiotics can predispose to joint inflammation, this phenomenon remains poorly understood. Here, we leverage mouse models of alphavirus-induced arthritis to investigate the roles of gut commensals, metabolites, and host immune mechanisms in promoting musculoskeletal inflammation. Mice treated with a short course of oral antibiotics exhibited worsened arthritis after chikungunya (CHIKV) or Mayaro virus infections. This phenotype was associated with loss of short chain fatty acids (SCFA), greater intestinal permeability, and activation of gut-associated immune cells, and required TLR4 signaling, MyD88 expression, monocytes, antigen-specific and bystander CD4+ T cells, and pro-inflammatory cytokines. Administration of exogenous SCFA or colonization of mice with bacterial species that generate SCFA mitigated CHIKV-induced joint inflammation. Single-cell RNA sequencing revealed that gut-derived SCFA ameliorate the inflammatory phenotype of synovial CD4+ T cells, infiltrating monocytes, and resident osteoclast-like cells. Thus, antibiotic-triggered gut dysbiosis exacerbates alphavirus arthritis by shaping the inflammatory profile of both infiltrating and resident immune cells in joint tissues.

immunology↗

bioRxiv2025

Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins

Chikungunya virus (CHIKV) infects both humans and mosquitoes during its transmission cycle. How the viruss envelope proteins mediate entry in cells from such different species is unclear. MXRA8 is a receptor for CHIKV in mammalian cells, but the receptor(s) in mosquito cells remains unknown. Here we use pseudovirus deep mutational scanning to measure how nearly all amino-acid mutations to the CHIKV envelope proteins affect entry in MXRA8-expressing human and mosquito cells. Most mutations similarly affect entry in both types of cells, and our comprehensive measurements of these effects define functional constraints related to protein folding and fusion activity. However, some mutations differentially affect entry in MXRA8-expressing human cells versus mosquito cells. Sites where mutations specifically impair entry in MXRA8-expressing human cells are often involved in MXRA8 binding, and we hypothesize sites where mutations specifically impair entry in mosquito cells are involved in binding the unknown mosquito receptor(s). We use the deep mutational scanning data to design loss-of-tropism mutant viruses that are impaired in their ability to infect either mosquito cells or MXRA8-expressing human cells. Our findings provide insights into the species-specific determinants of CHIKV cell entry that can help guide receptor identification and vaccine development.

microbiology↗

bioRxiv2025

LDL receptor-mediated endocytosis of Escherichia coli α-hemolysin mediates renal epithelial toxicity

Pore-forming toxins (PFTs) are secreted bacterial effector molecules that disrupt host cell membranes. The -hemolysin (HlyA) of uropathogenic Escherichia coli (UPEC) can exert damage to various mammalian cell types. While a candidate toxin receptor (CD11a/CD18 [LFA-1] integrin) exists on myeloid cells, the mechanism of HlyA cytotoxicity to epithelial cells remains undefined. We show that HlyA secretion by UPEC exacerbates renal tubular epithelial injury during ascending pyelonephritis in mice. A CRISPR-Cas9 loss-of-function screen in renal collecting duct cells identified clathrin-mediated endocytosis as required for HlyA cytotoxicity. HlyA internalization induces lysosomal permeabilization, facilitating protease release, cytoplasmic acidification, and mitochondrial dysfunction leading to rapid cell death. This mechanism contrasts with the described actions of other PFTs (plasma membrane poration and osmotic cytolysis). We also identify the low-density lipoprotein receptor (LDLR) as an epithelial receptor for HlyA; genetic or competitive inhibition of the HlyA-LDLR interaction prevented cytotoxicity. Our studies define a new mechanism of action for HlyA, in which its toxicity to epithelial cells requires LDLR-mediated, clathrin-dependent internalization. These results suggest therapeutic avenues for mitigating HlyA-induced damage during E. coli infections.

microbiology↗

bioRxiv2025

Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex

Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5 cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5 untranslated regions (UTRs), a characteristic of many viral mRNAs, can also serve as a molecular pattern for innate immune recognition via the interferon-induced proteins IFIT2 and IFIT3. The IFIT2-IFIT3 heterodimer, formed through an intricate domain swap structure resolved by cryo-EM, mediates viral mRNA 5 end recognition, translation inhibition, and ultimately antiviral activity. Critically, 5 UTR lengths <50 nucleotides are necessary and sufficient to sensitize an mRNA to translation inhibition by the IFIT2-IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5 UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2-IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size.

microbiology↗

bioRxiv2024

Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization. We show that 77.8% of the B cell clones in the GC expressed as representative monoclonal antibodies recognized the spike protein, with a third (37.8%) of these targeting the receptor binding domain (RBD). Strikingly, only one RBD-targeting mAb, mAb-52, neutralized all tested SARS- CoV-2 strains, including the recent KP.2 variant. mAb-52 utilizes the IGHV3-66 public clonotype, protects hamsters challenged against the EG.5.1 variant and targets the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Finally, we show that the remarkable breadth of mAb-52 is due to the somatic hypermutations accumulated within vaccine-induced GC reaction. One Sentence SummaryBooster SARS-CoV-2 mRNA vaccine recruits and broadens GC B cell responses targeting a highly conserved site on receptor binding domain of spike glycoprotein.

immunology↗

bioRxiv2024

Nanoparticle-Supported, Rapid, Digital Quantification of Neutralizing Antibodies Against SARS-CoV-2 Variants

The measurement of neutralizing immune responses to viral infection is essential, given the heterogeneity of human immunity and the emergence of new virus strains. However, neutralizing antibody (nAb) assays often require high-level biosafety containment, sophisticated instrumentation, and long detection times. Here, as a proof-of-principle, we designed a nanoparticle-supported, rapid, electronic detection (NasRED) assay to assess the neutralizing potency of monoclonal antibodies (mAbs) against SARS-CoV-2. The gold nanoparticles (AuNPs) coated with human angiotensin-converting enzyme 2 (ACE2) protein as nAb potency reporters were mixed with the mAbs to be tested, as well as streptavidin-conjugated multivalent spike (S) protein or their receptor binding domains (RBD). High-affinity and ACE2-competitive nAbs alter the S (or RBD)-to-ACE2 binding level and modulate AuNP cluster formation and precipitation. The amount of free-floating AuNP reporters is quantified by a semiconductor-based readout system that measures the AuNPs optical extinction, producing nAb signals that can differentiate SARS-CoV-2 variants (Wuhan-Hu-1, Gamma, and Omicron). The modular design nature, short assay time (less than 30 minutes), and portable and inexpensive readout system make this NasRED-nAb assay applicable to measuring vaccine potency, immune responses to infection, and the efficacy of antibody-based therapies.

immunology↗

bioRxiv2024

A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits pan neutralization of variants that evolved during the 4.5 years since the emergence of SARS-CoV-2 and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered post-exposure by an intranasal route. The resistance of TRI2-2 to viral escape and its direct delivery to the upper airways rationalize a path toward clinical advancement.

biochemistry↗

bioRxiv2024

Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain

Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg relative to a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain. IMPORTANCESequential boosting with mRNA vaccines has been effective strategy to overcome waning immunity and neutralization escape by emerging SARS-CoV-2 variants. However, it remains unclear how the site of boosting relative to the primary vaccination series shapes optimal immune responses or breadth of protection against variants. In K18-hACE2 transgenic mice, we observed that boosting with historical monovalent or variant-matched bivalent vaccines in the ipsilateral or contralateral limb elicited comparable levels of serum spike specific antibody and antigen-specific B and T cells responses. Moreover, boosting on either side conferred equivalent protection against a SARS-CoV-2 Omicron challenge strain. Our data in mice suggest that the site of boosting with an mRNA vaccine does not substantially impact immunity or protection against SARS-CoV-2 infection.

microbiology↗

bioRxiv2024

MXRA8 promotes adipose tissue whitening to drive obesity

Matrix-remodeling associated 8 (MXRA8), also known as Dual immunoglobulin domain cell adhesion molecule (DICAM), is a type 1 transmembrane protein that reportedly binds the V{beta}3 integrin1 and regulates the differentiation of osteoclasts2 and chondrocytes3, tumor growth4, T cell trafficking5, and angiogenesis6. MXRA8 is also an essential entry receptor for chikungunya virus and other related arthritogenic alphaviruses.7-9 We compared MXRA8 expression in 51 tissues in the Human Protein Atlas and found it is most highly expressed in white adipose tissue (WAT), however the function of MXRA8 in WAT is unknown. Here, we found that MXRA8 expression in WAT is increased in people with obesity and that this response is also observed in a mouse model of high fat-diet (HFD)-induced obesity. Single-nucleus RNA sequencing and high-dimensional spectral flow cytometry analyses revealed that MXRA8 is expressed predominantly by adipocyte progenitor (AP) cells and mature adipocytes. MXRA8 mutant primary adipocytes from inguinal (i)WAT exhibited increased expression of Uncoupling protein 1 (UCP1), a thermogenic protein expressed by beige and brown adipocytes that limits obesity pathogenesis.10-12 Indeed, MXRA8 mutant mice fed a HFD had preserved UCP1+ beige and brown adipocytes and were protected from HFD-induced obesity in a UCP1-dependent manner. Collectively, these findings indicate that MXRA8 promotes whitening of beige and brown adipose tissues to drive obesity pathogenesis and identify MXRA8 as a possible therapeutic target to treat obesity and associated metabolic diseases.

physiology↗

bioRxiv2024

Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2

Although vaccines have reduced COVID-19 disease burden, their efficacy in helminth infection endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal hookworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of SARS-CoV-2. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+ and CD8+ T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared to animals immunized without Hpb infection. Helminth mediated suppression of spike-specific CD8+ T cell responses occurred independently of STAT6 signaling, whereas blockade of IL-10 rescued vaccine-induced CD8+ T cell responses. In mice, intestinal helminth infection impairs vaccine induced T cell responses via an IL-10 pathway and compromises protection against antigenically shifted SARS-CoV-2 variants.

immunology↗

bioRxiv2024

Prototype mRNA vaccines imprint broadly neutralizing human serum antibodies after Omicron variant-matched boosting

Immune imprinting is a phenomenon in which an individuals prior antigenic experiences influence responses to subsequent infection or vaccination. Here, using antibody depletion and multiplexed spike-binding assays, we characterized the type-specificity and cross-reactivity of serum antibody responses after mRNA vaccination in mice and human clinical trial participants. In mice, a single priming dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike minimally imprinted serum responses elicited by Omicron boosters, enabling a robust generation of type-specific antibodies. However, substantial imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron mRNA vaccine. In humans who received two BA.5 or XBB.1.5 Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with circulating Omicron variants as well as more distantly related sarbecoviruses. Because the serum neutralizing response against Omicron strains and other sarbecoviruses was completely abrogated after pre-clearing with the Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes shaped and shared by the antecedent mRNA-1273 primary series. Our depletion analysis also identified cross-reactive neutralizing antibodies that recognize distinct epitopes in the receptor binding domain (RBD) and S2 proteins with differential inhibitory effects on members of the sarbecovirus subgenus. Thus, although the serum antibody response to Omicron-based boosters in humans is dominantly imprinted by prior immunizations with prototype mRNA-1273 vaccines, this outcome can be beneficial as it drives expansion of multiple classes of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and extend activity to distantly related sarbecoviruses.

immunology↗