CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Long, Y.; Sun, J.; Liu, T.; Tang, F.; Zhang, X.; Qin, Q.; Miao, Y.; Pan, X.; An, Q.; Qin, M.; Tong, X.; Peng, X.; Yu, P.; Zhu, P.; Zhu, W.; Zhang, Y.; Zhang, L.; Xiao, G.; Zuo, J.; Tang, W.; Zhou, J.; Xu, Z.; Gan, Y.; Ren, J.; Huang, W.; Jin, G.; Gong, L.

doi:10.1101/2021.04.10.439275

bioRxiv · 10.1101/2021.04.10.439275

CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Long, Y.·Sun, J.·Liu, T.·Tang, F.·Zhang, X.·Qin, Q.·Miao, Y.·Pan, X.·An, Q.·Qin, M.·Tong, X.·Peng, X.·Yu, P.·Zhu, P.·Zhu, W.·Zhang, Y.·Zhang, L.·Xiao, G.·Zuo, J.·Tang, W.·Zhou, J.·Xu, Z.·Gan, Y.·Ren, J.·Huang, W.·Jin, G.·Gong, L.

View original source ↗Export metadata ↓

Abstract

Safe, economical and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and halt the pandemic. We have constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains two immunodominant peptides screened from receptor-binding domain (RBD) and is fully chemically synthesized. And the vaccine has optimized nanoemulsion formulation, outstanding stability and safety. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of RBD-specific and protective neutralizing antibodies (NAbs), which were also effective to RBD mutations. CoVac501 was found to elicit the increase of memory T cells, antigen-specific CD8+ T cell responses and Th1-biased CD4+ T cell immune responses in NHPs. More importantly, the sera from the immunized NHPs can prevent infection of live SARS-CoV-2 in vitro. One-Sentence SummaryA novel SARS-CoV-2 vaccine we developed, CoVac501, which is a fully chemically synthesized and self-adjuvanting peptides conjugated with TLR7 agonists, can induce high-efficient humoral and cellular immune responses against SARS-CoV-2.

Source connections

Published article ↗

Explore related subjects

immunology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Long, Y., Sun, J., Liu, T., Tang, F., Zhang, X., Qin, Q., Miao, Y., Pan, X., An, Q., Qin, M., Tong, X., Peng, X., Yu, P., Zhu, P., Zhu, W., Zhang, Y., Zhang, L., Xiao, G., Zuo, J., Tang, W., Zhou, J., Xu, Z., Gan, Y., Ren, J., Huang, W., Jin, G., Gong, L.. 2021-04-11. CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity. https://doi.org/10.1101/2021.04.10.439275

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Exploratory positional differences in observed CDRH2 lineage-state transitions following HIV-1 germline-targeting vaccination

Background: Germline-targeting HIV-1 vaccination recruits VRC01-class B-cell precursors, but the positional patterns of observed longitudinal B-cell receptor lineage-state changes remain incompletely described. We compared CDRH2 profiles between homologous and heterologous boosting regimens using published IAVI G002 data. Methods: Participant-specific Week-8 lineages were prospectively matched to Week-24 observations. Germline-to-nongermline changes in sampled lineage-modal residues were evaluated at seven IGHV1-2*02 CDRH2 positions using participant-balanced, mean-centered profiles and exact participant-label permutation inference. Sampling-depth and sorting-probe sensitivity analyses assessed observability. A separate participant-held-out benchmark evaluated antibody-language-model representations for predicting observed Week-24 lineage detection. Results: The CDRH2 analysis included 332 lineages, 15 participants, 2,179 eligible lineage-position observations, and 241 observed state changes. The regional profile statistic was 0.027066 (exact p = 0.001709; six-region adjusted q = 0.010256), with descriptive differences at V-relative positions 51, 54, and 55. Most eligible longitudinal observations had one assessable cell per visit. In seven Group-1 participants, Week-24 dual-probe sampling recovered 181 baseline lineages with eOD-GT8 and 143 with Cg28v2, including 60 detected by both probes. In a separate cohort of 2,739 lineages from 17 participants, IgBERT and AbLang-2 representations did not improve participant-balanced average precision over a four-feature biological baseline. Conclusions: Observed CDRH2 lineage-modal-state profiles differed between regimens in this exploratory secondary analysis. Sparse sampling, potentially probe-related ascertainment, and absent linked functional validation preclude inference about mutation timing, functional improvement, or causal booster effects.

immunology↗

bioRxiv2026

Multivalent mRNA tuberculosis vaccines protect against mycobacterial infection in zebrafish, mice and guinea pigs

Despite a century of BCG use, tuberculosis remains a leading cause of death from infectious diseases and more effective vaccines are urgently needed. Here we combined antigen discovery in zebrafish with mRNA vaccine technology to generate multivalent vaccine candidates, TUmRNA4, TUmRNA6 and TUmRNA9, encoding four, six, or nine Mycobacterium tuberculosis antigens, respectively. The vaccines were well tolerated, and induced robust antigen-specific cellular immune responses, including IFN{gamma} production and expansion of memory T-cell populations. In mice, TUmRNA4 and TUmRNA6 reduced pulmonary M. tuberculosis burden and lung pathology to levels comparable to BCG vaccination and TUmRNA6 enhanced BCG-mediated protection when used as a booster vaccine. In guinea pigs, TUmRNA9 reduced bacterial burden in the lungs, spleen, and lymph nodes and decreased pulmonary lesions. These findings demonstrate that protective antigens identified in zebrafish can be translated into effective multivalent mRNA vaccines and establish a framework for tuberculosis vaccine development across multiple preclinical models.

immunology↗

bioRxiv2026

AlphaScreen profiling of extracellular vesicle-associated platelet, immune, and vascular markers reveals disease-specific signatures in ME/CFS, fibromyalgia, and long COVID

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and long COVID (LC-19) are chronic diseases with overlapping clinical features and poorly understood pathophysiology. Increasing evidence suggests the involvement of immune dysregulation, endothelial dysfunction, and altered vascular physiology. Extracellular vesicles (EVs) are key mediators of intercellular communication and are envisioned as sensors of homeostasis and disease. The aim of this study was to determine whether EV marker profiling could provide a basis for the differential diagnosis of ME/CFS, FM and LC-19 and/or patient stratification. Methods: EV-enriched plasma from ME/CFS, FM, cases co-diagnosed with ME/CFS and FM, LC-19 patients, and matched healthy controls (n = 10 per study group) were analyzed. EV concentration and size distribution were assessed by nanoparticle tracking analysis, followed by targeted profiling of EV-associated surface markers via AlphaScreen, including tetraspanins CD9 and CD63, platelet- (CD41/CD61), myeloid- (CD13), immune- (CD74 and CX3CR1), and renin-angiotensin system- associated ACE1 (also known as CD143), and ACE2 surface markers. Results: The studied disease groups presented distinct EV signatures. LC-19 samples exhibited the most pronounced and coordinated alterations, characterized by increased levels of CD9/CD74, CD9/CX3CR1, and CD9/ACE1-positive EVs, along with reduced overall particle concentrations. Notably, platelet-derived CD9/CD41/CD61-positive EVs were significantly elevated in both LC-19 and ME/CFS, as compared to healthy controls, indicating enhanced platelet activation. Immune-associated markers revealed differential pathway activation in LC-19, with CD74-positive EVs reflecting antigen presentation and inflammatory signaling, and CX3CR1-positive EVs indicating altered leukocyte trafficking and vascular interaction. Increased ACE1-positive EVs in LC-19 further suggested a shift toward pro-inflammatory renin-angiotensin signaling. Conclusion: Collectively, these findings support a disease-specific dysregulation of platelet, immune, and vascular pathways. The integrated EV signatures distinguish LC-19 from the related chronic conditions ME/CFS and FM, highlighting the potential of EV-based profiling for differential diagnosis. Our results provide a systems-level perspective on the differential pathophysiology of these disorders and identify EV-associated markers as candidate biomarkers with clinical value.

immunology↗