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

Baoling Ying,

Chieh-Yu Liang, Pritesh Desai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 7, 2024

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

Language: Английский

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions DOI Creative Commons

C. Pierre,

Lily E. Adams, Jaclyn S. Higgins

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(6), P. e1011569 - e1011569

Published: June 20, 2024

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice cynomolgus macaques from severe disease. The mechanisms of NTD antibody-mediated protection are unknown. Here we show Fc mediate (non-nAb) MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious titers lung as potently (nAb) infusion, disease markers including gross discoloration were similar nAb groups. functional knockout substitutions abolished increased group. enhancement relative WT, supporting a positive association between functionality degree infection. For therapeutic administration antibodies, contributed virus suppression lessening discoloration, but presence neutralization required for optimal This study demonstrates non-nAbs can utilize Fc-mediated lower load prevent damage due coronavirus

Language: Английский

Citations

12
Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates DOI Creative Commons
Matthew Gagné, Barbara J. Flynn, Shayne F. Andrew

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(10), P. 1913 - 1927

Published: Sept. 3, 2024

Abstract A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 BA.5 spike proteins or a WA1–BA.5 chimpanzee adenoviral-vectored vaccine delivered by intranasal aerosol device. NHPs boosted either had minimal virus nose lungs, respectively. By contrast, was limited to lower airways. The mucosally elicited durable airway IgG IgA responses and, unlike vaccine, induced spike-specific B cells lungs. IgG, T cell correlated whereas alone upper protection. This study highlights differential serum correlates how vaccines can durably SARS-CoV-2.

Language: Английский

Citations

10
Intranasal SARS-CoV-2 Omicron variant vaccines elicit humoral and cellular mucosal immunity in female mice DOI Creative Commons
Stefan Slamanig, Irene González‐Domínguez,

Lauren A Chang

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 105, P. 105185 - 105185

Published: June 7, 2024

In order to prevent the emergence and spread of future variants concern severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing vaccines capable stopping transmission is crucial. The SARS-CoV-2 vaccine NDV-HXP-S can be administered live intranasally (IN) thus induce protective immunity in upper tract. based on Newcastle disease virus (NDV) expressing a stabilised spike protein. produced as influenza at low cost embryonated chicken eggs.

Language: Английский

Citations

8
Harnessing T-Cells for Enhanced Vaccine Development against Viral Infections DOI Creative Commons
Zhen Zhuang, Jianfen Zhuo,

Yaochang Yuan

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 478 - 478

Published: April 29, 2024

Despite significant strides in vaccine research and the availability of vaccines for many infectious diseases, threat posed by both known emerging diseases persists. Moreover, breakthrough infections following vaccination remain a concern. Therefore, development novel is imperative. These must exhibit robust protective efficacy, broad-spectrum coverage, long-lasting immunity. One promising avenue lies leveraging T-cells, which play crucial role adaptive immunity regulate immune responses during viral infections. T-cell recognition can target highly variable or conserved proteins, memory T-cells offer potential durable Consequently, T-cell-based hold promise advancing efforts. This review delves into latest advancements across various platforms discusses associated challenges.

Language: Английский

Citations

4
Systemic and Mucosal Immunogenicity of Monovalent XBB.1.5-Adapted COVID-19 mRNA Vaccines in Patients with Inflammatory Bowel Disease DOI Creative Commons
Simon Woelfel,

Joel Dütschler,

Daniel Junker

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(7), P. 774 - 774

Published: July 15, 2024

Recently updated COVID-19 mRNA vaccines encode the spike protein of omicron subvariant XBB.1.5 and are recommended for patients with inflammatory bowel disease (IBD) on immunosuppressive treatment. Nonetheless, their immunogenicity in IBD against rapidly expanding virus variants remains unknown. This prospective multicenter cohort study is first to investigate XBB.1.5-adapted IBD. Systemic mucosal antibodies targeting receptor-binding domains (RBDs) subvariants XBB.1.5, EG.5.1, BA.2.86, as well neutralization were quantified before two four weeks after vaccination monovalent vaccines. Vaccination increased levels serum anti-RBD IgG BA.2.86 (1.9-fold, 1.8-fold, 2.6-fold, respectively) enhanced corresponding responses (2.3-fold, 3.1-fold, 3.5-fold, respectively). Following vaccination, anti-TNF-treated had reduced compared treatments other cellular targets. 11.1% 16.7% lacked EG.5.1 neutralization, respectively; all these received anti-TNF At sites, induced variant-specific but failed induce RBD-targeting IgA. Our findings provide a basis future vaccine recommendations while highlighting importance frequent booster adaptation need strategies

Language: Английский

Citations

4
Intranasal Administration of Bivalent RBD Nanoparticles Elicits Strong Systemic Responses That Effectively Block Distal Dissemination of COVID‐19 DOI Open Access

Mathurin Seesen,

Panya Sunintaboon,

Jitra Limthongkul

et al.

Microbiology and Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

The intranasal vaccine against coronavirus disease 2019 (COVID-19) has gained more attention because of its ability to induce both mucosal and systemic immune responses. We have recently developed a c-GAMP-adjuvanted bivalent receptor-binding domain (RBD) vaccine, derived from the ancestral strain Omicron variant. demonstrated here that administration this candidate triggers not only respiratory but also response SARS-CoV-2. immunized mice elicited broadly neutralizing antibodies (Wuhan-1) variants concern (Delta, BA.1, BA.5). This route vaccination induced potent T cell responses with strong cytotoxic activity Wuhan-1 BA.1 strains. Additionally, intranasally significantly suppressed SARS-CoV-2 RNA levels in circulation spleens, indicating effective containment virus beyond tract. These findings suggest RBD holds promise for combating infections.

Language: Английский

Citations

0
SARS-CoV-2 spike protein is a self-adjuvanted antigen for mucosal immunization and confers broad protection against lethal challenge with SARS-CoV-2 via intranasal vaccination DOI Creative Commons

Ping Zhao,

Zhendong Pan,

Zheng Xu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Abstract Effective respiratory mucosal vaccines are urgently needed to control the rapid mutation and spread of SARS-CoV-2. In this respect, most focused virus vector-vaccine adjuvanted recombinant vaccine strategies face safety effectiveness concerns. Here, we revealed that spike protein (S-2P) original SARS-CoV-2 strain is a self-adjuvanted antigen for intranasal immunization can elicit potent systemic (serum IgG neutralizing antibodies splenic T-cell responses S1 S2 proteins) immunity (respiratory tract IgA responses) in absence an adjuvant. contrast, with hemagglutinin (HA) influenza H1N1 failed induce detectable serum antibodies. Furthermore, S-2P K18-hACE2 mice provided complete protection against lethal challenge 60% or 40% survival Omicron BA.5 EG.5, respectively. The immune induced by were significantly enhanced lentinan (LNT), immunomodulator used clinic, completely protected from EG.5 conferred additional protective mechanisms independent CD8 + T cells. Compared HA, robustly activated type I IFN signaling in vitro vivo, importantly, antibody response HA when it was simultaneously intranasally vaccinated HA. Mechanistically, integrins STING critically involved S-2P-eliciting via vaccination. Our findings demonstrate potential plus LNT as safe broad-spectrum variants.

Language: Английский

Citations

0
Xenogenic adenoviral vectors as vaccines DOI
Lynda Coughlan

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 309 - 364

Published: Jan. 1, 2025

Citations

0
Mucosal adenovirus vaccine Ad5-XBB.1.5 boosting elicits nasal IgA and transiently prevents JN.1 wave infection for less than 6 months in real-world settings DOI Creative Commons

Yanqun Wang,

Peilan Wei,

Jun Zhang

et al.

hLife, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Single-Dose Intranasal Immunization with ChAd68-Vectored Prefusion F Vaccines Confers Sustained Protection Against Respiratory Syncytial Virus in Murine Models DOI Creative Commons
Jing Miao, Xuejie Li, Y.M. Li

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(5), P. 528 - 528

Published: May 15, 2025

Background/Objectives: Respiratory syncytial virus (RSV) poses a substantial global health threat, particularly impacting infants and vulnerable pediatric populations through severe respiratory morbidity. Methods: We developed novel adenoviral vector vaccine platform utilizing chimpanzee adenovirus 68 (AdC68) to deliver prefusion F (pre-F) antigens from RSV subtypes A B, generating three candidates: AdC68-A (subtype A), AdC68-B B), AdC68-A+B (bivalent formulation). Results: Single intranasal (i.n.) immunization prime–boost immunizations via intramuscular (i.m.) routes in BALB/c mice induced robust immune activation, with single i.n. administration conferring durable protection evidenced by an 85% reduction pulmonary viral loads (p < 0.05) at 134 days post-immunization. All formulations elicited potent subtype-specific IgG responses (geometric mean titers 50–12,800) Th1-polarized cellular immunity (552–1201 IFN-γ+ spot-forming units/106 PBMCs, IgG2a/IgG1 > 1) bivalent formulation group, while i.m. boosting enhanced 3-fold versus prime alone 0.01). Notably, despite undetectable serum-neutralizing antibodies absent mucosal IgA bronchoalveolar lavage 7 post-i.n. immunization, the sustained control highlights non-neutralizing antibody-mediated protective mechanisms. Conclusions: These findings establish proof-of-concept for adenoviral-vectored vaccines against RSV, though optimization of humoral response induction duration require further investigation.

Language: Английский

Citations

0