bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.08.30.458307

Immunogenicity and efficacy of Heat Inactivated Whole-Cell Vaccine to increase murine survival after Extensively drug-resistant Acinetobacter baumannii infection.

Sharmin, N.·Khoda, M. E.·Shamsuzzaman, S. M.·Uddin, M. N.
View original source ↗Export metadata ↓

Abstract

Due to the rapid emergence of extensively drug-resistant (XDR) strains worldwide there is a necessity for greater consideration for the role of preventive vaccines to combat these pathogens. The study reported the effectiveness of a heat-inactivated whole-cell vaccine (HI-WCV) against A. baumannii to produce protective immunity with evaluation of the bactericidal antibody responses in mice after intramuscular inoculation with different XDR strains of A. baumannii. Six XDR A. baumannii strains emulsified with complete freunds adjuvant (CFA) were used for intramuscular inoculation in the experimental group of mice (n=4) in three different phases on 14 days interval whereas placebo-controlled mice (n=4) received phosphate-buffered saline emulsified with CFA in same the schedule. Serum was collected from tail blood of each mouse on 10th day after each inoculation and by cardiac puncture on 14th day after lethal dose from the experimental group and after death of the placebo-controlled group. Mice inoculated with heat-inactivated whole-cell vaccine survived and showed a higher neutralizing (IgG) antibody response after 2nd (>7-fold titre) and 3rd inoculation (>12-fold titre) whereas all mice from placebo-controlled group did not survived. Sera from experimental group of mice collected (38th day) after 3rd inoculation resulted in higher serum bactericidal killing index (42.12) after three hours incubation with an XDR A. baumannii over sera collected after 1st and 2nd inoculation (50% cutoff value=14.5). These results suggest that intramuscular vaccination with heat-inactivated whole-cell vaccine stimulated IgG antibody responses that can increase murine survival after XDR A. baumannii infection.

Source connections

Explore related subjects

immunologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sharmin, N., Khoda, M. E., Shamsuzzaman, S. M., Uddin, M. N.. 2021-08-31. Immunogenicity and efficacy of Heat Inactivated Whole-Cell Vaccine to increase murine survival after Extensively drug-resistant Acinetobacter baumannii infection.. https://doi.org/10.1101/2021.08.30.458307

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

KEEP EXPLORING

Related preprints

bioRxiv2026

ACE-engineered human iPSC-derived neutrophils enhance host defense against multidrug-resistant bacterial infections

Severe neutropenia predisposes patients to life-threatening infections, while donor-dependent granulocyte transfusions are limited by availability and variable cell quality. Here, we engineered human induced pluripotent stem cells (iPSCs) to constitutively or inducibly express angiotensin-converting enzyme (ACE) and differentiated them into functional ACE-engineered neutrophils (ACE-iNeu). ACE expression enhanced granulocytic maturation, reactive oxygen species generation, inflammatory cytokine production, and antimicrobial signaling. ACE-iNeu exhibited enhanced bactericidal activity against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. Following adoptive transfer into neutropenic mice, ACE-iNeu significantly reduced circulating and tissue bacterial burdens. Integrated metabolomic and transcriptomic analyses revealed ACE-associated alterations in adenine nucleotide abundance and developmental and inflammatory pathways. Together, these findings establish ACE engineering as a strategy to enhance the production and antimicrobial function of human iPSC-derived neutrophils and support further preclinical development of engineered granulocyte therapies for severe drug-resistant infections.

immunology↗
bioRxiv2026

Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and protection in mice.

An effective dengue vaccine must establish durable immunity across four dengue virus (DENV) serotypes, evade antibody-dependent enhancement (ADE), and overcome immune imprinting from prior exposure. Here, we developed TetprM-E mRNA-LNP, a tetravalent vaccine comprising LNP-formulated nucleoside-modified mRNAs encoding DENV1-4 precursor membrane-envelope (prM-E) antigens, and evaluated its immunogenicity, durability, protection and breath across serotype-specific immune backgrounds. Three immunization strategies elicited neutralizing titers greater than 1:1500 against each serotype. Passive transfer of immune sera conferred 100% survival and reduced viremia after lethal DENV2 challenge in immunocompromised mice. Vaccination induced DENV envelope (env)-specific CD8+T cells and CD4-dependent germinal-center responses. DENV env-binding antibodies persisted for 34 weeks alongside DENV env-specific memory B cells. Vaccine-elicited sera showed no measurable in vitro ADE. Although monovalent priming initially biased antibody responses, TetprM-E mRNA-LNP vaccination broadened neutralization across DENV1-4 regardless of priming serotype. Together, TetprM-E mRNA-LNP elicits broad, durable, and protective immunity despite serologic constraints from pre-existing immunity.

immunology↗
bioRxiv2026

The antagonism of sex chromosomes and sex hormones dictates outcomes in Th17 cell-mediated central nervous system autoimmunity.

Biological sex traits are shaped by the combined effects of both sex hormones and chromosomes. How these factors interact in sex-related autoimmune diseases, such as multiple sclerosis (MS), has been a subject of intense recent interest. Here, using the Four Core Genotype (FCG) mouse model, in which these two variables can be disentangled, we describe an antagonism between sex hormones and chromosomes that potently influences outcomes in T helper 17 (Th17)-driven progressive central nervous system (CNS) autoimmunity. Male gonadal hormones dampen disease severity, irrespective of sex chromosome complement, by promoting a Wnt/{beta}-catenin signaling program associated with a homeostatic, non-pathogenic Th17 phenotype. By contrast, XY chromosomal complement exacerbates Th17 pathogenicity in a recipient sex-dependent manner; we identify the X-linked molecule SUV39H1 as an inhibitor of inflammatory Th17 cell function. Unexpectedly, we found that hormonally and chromosomally female FCG Th17 cells induced far more severe disease than WT female counterparts despite being genetically identical, pointing to a parental imprinting effect in dictating Th17 cell pathogenicity. These latter investigations uncovered Runx2, a transcription factor previously linked to developmental programs, as a novel negative regulator of the pathogenicity of Th17 cells. Together, our findings establish biological sex as a multilayered regulator of Th17 pathogenicity, revealing distinct and sometimes opposing contributions of hormones, chromosomes, and parental inheritance.

immunology↗