Human cytomegalovirus (HCMV) can cause life-threatening infection in immunosuppressed patients, and infection that may lead to birth defects. No vaccine is currently available. HCMV infection in healthy subjects is generally asymptomatic, and virus persists as latent infection for life. Host immunity is effective against reactivation and super-infection with another strain. Thus, vaccine candidates able to elicit immune responses similar to those of natural infection may confer protection. Since neutralization is essential for prophylactic vaccines, it is important to understand how antiviral antibodies are developed in natural infection. We hypothesized that the developmental path of antibodies in seropositive subjects could be unveiled by interrogating host B-cell repertoires using unique genetic signature sequences of mAbs. Towards this goal, we isolated 56 mAbs from three healthy donors with different neutralizing titers. Antibodies specific to the gH/gL/pUL128/130/131 pentameric complex were more potent in neutralization than those to gB. Using these mAbs as probes, patterns of extended lineage development for B-cells and evidence of active antibody maturation were revealed in two donors with higher neutralizing titers. Importantly, such patterns were limited to mAbs specific to the pentamer, but none to gB. Thus, memory B-cells with antiviral function such as neutralization were active during latent infection in the two donors, and this activity was responsible for their higher neutralizing titers. Our results indicated that memory B-cells of neutralizing capacity could be frequently mobilized in host, probably responding to silent viral episodes, further suggesting that neutralizing antibodies could play a role in control of recurrent infection.
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http://dx.doi.org/10.18632/oncotarget.18359 | DOI Listing |
Heliyon
July 2024
Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Immunocompromised children are at risk of developing severe COVID-19 infection. We conducted a pilot prospective study to evaluate the impact of cancer treatment and stem cell transplantation on immunogenicity of two doses of BNT162b2 vaccine in pediatric patients. Humoral, B- and T-cell responses to the BNT162b2 vaccine were assessed before, after the first and the second dose in patients aged 5-12 years (n = 35) and in a group of healthy donors (HD, n = 12).
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
B lymphocytes (B cells) are a type of white blood cell that play an essential role in the adaptive immune response. They are derived from pluripotent hematopoietic stem cells and undergo several developmental stages in the bone marrow and secondary lymphoid organs to become effector cells. B cells can act as antigen-presenting cells, secrete cytokines, generate immunological memory as memory B cells, and produce and secrete high-affinity antibodies as plasma B cells.
View Article and Find Full Text PDFNPJ Vaccines
December 2024
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Eilat (EILV)/chikungunya virus (CHIKV), an insect-based chimeric alphavirus was previously reported to protect mice months after a single dose vaccination. The underlying mechanisms of host protection are not clearly defined. Here, we assessed the capacity of EILV/CHIKV to induce quick and durable protection in cynomolgus macaques.
View Article and Find Full Text PDFHeliyon
December 2024
Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Monoclonal antibody (mAb) technology has significantly contributed to basic research and clinical settings for various purposes, including protective and therapeutic drugs. However, a rapid and convenient method to generate high-affinity antigen-specific mAbs has not yet been reported. Here, we developed a rapid, easy, and low-cost protocol for antigen-specific mAb production from single memory B cells.
View Article and Find Full Text PDFPNAS Nexus
December 2024
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies in nonhuman primates (NHPs) comparing the most common clinical adjuvant aluminum hydroxide (alum) with saponin/monophosphoryl lipid A nanoparticles (SMNP), an immune-stimulating complex-like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum, including 7-fold higher peak antigen-specific germinal center B-cell responses, 18-fold higher autologous neutralizing antibody titers, and higher levels of antigen-specific plasma and memory B cells.
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