bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing defined structural subunits to elucidate antibody populations elicited by a recombinant subunit Ebola virus vaccine
Authors: Ball Aquena H , Lehrer Axel T 
Published: January 2023

Abstract
Ebola virus (EBOV) causes lethal hemorrhagic fevers with case fatality rates of up to 90%. The recent large outbreak in West Africa and current outbreak in the DRC demonstrate an obvious need for vaccines and therapeutics. All vaccine candidates use the surface glycoprotein as the main antigen. However, the method of protection induced by the EBOV glycoprotein remains unclear. The EBOV glycoprotein is composed of GP1 and GP2 linked by a disulfide bond. GP1 contains the receptor binding domain, glycan cap, and the heavily glycosylated mucin-like domain while GP2 contains the fusion loop and transmembrane anchor. We have developed a subunit vaccine that allows for an increased safety profile as well as shows increased thermostability, which allows easier deployment in central Africa. With our studies we expect to reveal antibody patterns differentiating survivors and non-survivors from non-human primate studies as well as reveal subdomains that are more protective and/or immunodominant to guide future vaccine development as well as provide insights into correlates of protection.
Subunits of the EBOV glycoprotein have been produced in Drosophila S2 cells including full length GP, GPΔmucin-like domain, GP1, GP2, and sGP. These subdomains will be used to explore the binding patterns of antibodies elicited by a highly purified GP subunit vaccine. Ongoing analysis focuses on samples from non-human primates immunized with 3 doses of EBOV GP + adjuvant that will be analyzed for antigen binding IgG to differentiate the pre-challenge antibody binding patterns to the different EBOV subdomains.
Comparison of antibody responses in mice generated by different multivalent Filovirus vaccines based on recombinant glycoprotein subunits
Authors: Tashiro Taylor E , Wong Teri Ann , Lehrer Axel T 
Published: January 2023

Abstract
Filoviruses cause fulminant hemorrhagic fevers with case-fatality rates up to 90%. Recombinant glycoprotein (GP) derived from Ebola virus (EBOV), Sudan virus (SUDV) and Marburg virus (MARV) have been expressed from stably transformed Drosophila S2 cells and used to formulate recombinant subunit vaccine candidates showing efficacy in rodents and non-human primates. Immunogenicity of 11 different formulations of our trivalent subunit vaccine with adjuvant was tested.
Each group of Swiss Webster mice was administered a formulation with or without adjuvant. Mouse sera were collected two weeks after 2nd and 3rd vaccine doses and diluted 1:8,000 and 1:40,000 to determine titers of IgG binding to EBOV, SUDV and MARV GP by a microsphere immunoassay (MIA). MFI (median fluorescence intensity) was collected by Luminex xPonent software then graphed and statistically analyzed using GraphPad Prism.
As expected, groups administered equal amounts of EBOV, SUDV, and MARV GP had the most balanced antibody response as compared to groups that did not receive equal amounts of GP. Formulations with optimal antigen doses generate balanced antigen-binding antibody responses. Additional experiments are ongoing including the characterization of virus neutralization activity of the different formulations.
Characterization of immune response in mice vaccinated with highly efficacious vaccine 0ΔNLS against HSV-1
Authors: Gmyrek Grzegorz Bogdan , Carr Daniel J.J. 
Published: January 2023

Abstract
Using an experimental mouse model we compared the host immune response of a mutant HSV-1, termed 0ΔNLS (deficient in the nuclear location signal of ICP0), a highly efficacious prophylactic vaccine against ocular HSV-1 infection, to that of the parental HSV-1 virus, termed GFP105 (KOS background). C57BL/6 mice were infected in the footpad (FP) with 1×105 plaque forming units of virus and at times post infection (PI), organized lymphoid tissues were analyzed for changes in the immune profile. 0ΔNLS infected animals were more efficient in clearance of virus from the FP and generated a more robust chemokine responses and myeloid cell infiltration in FP at early time points (day 1–3 PI) compared to GFP105 infected mice. By day 7 PI, there were significantly more GC B cells and isotype switched B cells in the PLN of mice infected with 0ΔNLS in comparison to GFP105 infected animals. In addition, an increased number of follicular helper CD4 T cells along with enhanced IL-21 cytokine production and an increased number of antigen-specific CD8 T cells against major and sub-major HSV-1 epitopes was noted. In contrast, by day 21 PI, no difference in T cell and B cell subset was found in the PLN comparing the two groups of infected mice. Furthermore, mice which were re-exposed to 0ΔNLS 21 days PI showed an increased number of metabolically active plasma cells from the bone marrow and secretion of IgG by memory B cells after pre-activation compared to those re-infected with GFP105. In addition, an increased number of IFN-ɤ secreting, HSV-1-specific CD8 T cells from the re-exposed 0ΔNLS mice was observed as well. Collectively, these results warrant further studies to fully understand the efficacy of the 0ΔNLS virus as an effective vaccine against ocular HSV-1 infection.
Suppression of HBV replication in mice using stem cell-derived viral antigen-specific T lymphocytes
Authors: Song Jim Jianxun , Xiong Xiaofang 
Published: January 2023

Abstract
The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the hepatitis B virus (HBV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the liver to suppress HBV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs provoke the antiviral response remain to be fully elucidated. In this study, we generated the functional HBV surface Ag-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the underlying mechanisms of the CTL-mediated antiviral replication in a murine model. A hydrodynamic injection of an HBV expression plasmid, pAAV/HBV1.2, into the liver induced HBV replication in mice. We show that adoptive transfer of HBV surface Ag-specific iPSC-CTLs greatly suppressed the HBV replication in the liver and blood in the animal model and prevented the HBV surface Ag expression on hepatocytes. Furthermore, we demonstrate that the adoptive transfer significantly increased the migration of CD8+ T cells and the production of the antiviral cytokines (IFN-g, TNF-a) in the liver. These results indicate that the stem cell-derived tissue-associated CTLs can robustly accumulate in the liver and suppress the HBV replication through producing antiviral cytokine.
Lymph node and circulating TFH cells support SIV-specific antibody responses in peripheral blood and genital tract of vaccinated female rhesus macaques
Authors: Hait Sabrina Helmold , Hogge Christopher , Mushtaq Zuena , Hoang Tanya , Robert-Guroff Marjorie 
Published: January 2023

Abstract
TFH cells are critical for Ag-specific B cell selection in germinal centers (GCs). Circulating blood CXCR5+ CD4+ T cells (cTFH) were implicated in development of broadly neutralizing antibodies in HIV+ patients. We asked if an SIV vaccine regimen could induce GC TFH and cTFH cells that supported anti-SIV humoral immunity. Female rhesus macaques (RM) were primed twice mucosally with replicating Ad5hr-SIV recombinants (wks0&13) and boosted twice intramuscularly with SIVgp120 proteins (wks26&38). Blood, lymph nodes (LN), bone marrow (BM), vaginal and rectal swabs were collected pre-vaccination, post-2nd prime and post-2nd boost for TFH and B cell assessment. Total TFH, and Env-specific GC TFH cells and Env-specific memory (ESM) B cells were seen at wk38+3d, suggesting vaccine-mediated GC maturation. Env-specific LN TFH cells and GC B cells at wk13+3d correlated respectively with Env-specific rectal IgA and vaginal IgG titers at wk16. GC B cells and ESM B cells at wk38+3d correlated with Env-specific vaginal IgG and rectal IgA titers at wk41 respectively, indicating early GC formation contributed to SIV-specific immunity in the female genital tract (FGT). Env-specific cTFH cells peaked post-boosting and positively correlated with Env-specific IgA and IgG secreting plasmablasts and plasma cells in BM and rectal IgA titers. cTFH cells induced CD38 and CD138 upregulation in autologous B cells and supported IgA secretion in cocultures compared to B cells cultured alone or with non-cTFH cells. Our data indicate the prime/boost regimen induced GC TFH and cTFH cells, enabling robust anti-SIV T-cell-dependent mucosal and systemic B cell responses. Both LN and circulating TFH cells may play pivotal roles in FGT protective humoral immunity.
gdT cells stimulated by a novel vaccine confer protection to the naïve mice against S. aureus challenge
Authors: HUANG JIANDONG , Wang Xiaolei , Zhang Baozhong , Deng Jian , Yuen Kwok-yung 
Published: January 2023

Abstract
Staphylococcus aureus (S. aureus) is a common pathogen found in the community and in hospitals. Most notably, Methicillin-resistant S. aureus is resistant to many antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments such as immunotherapeutic approaches. Prophylactic vaccination is the best approach to combat against MRSA since it can provide protection without any concerns regarding antibiotic resistance. To date, most clinical trials of vaccines or passive immunization against S. aureus have ended in failure. In this study, we investigated multiple proteins as possible targets for a vaccine. Mice vaccinated with these purified proteins elicited high titers of specific antibodies as well as Th1- and Th17-biased immune responses in mice. Animal test indicated a protection rate over 90% in several animal models against multiple strains of S. aureus. Interestingly, gdT cells transferred from the vaccinated mice to naïve mice can confer protection to the naïve mice against S. aureus challenge in skin infection models. These findings raise the hope that the candidate antigens could be developed into multivalent and serotype-independent vaccines against S. aureus infection.
Application of a Campylobacter jejuni mouse infection model to test efficacy of a C. jejuni capsule conjugate vaccine delivered with a potent liposome adjuvant containing monophosphoryl lipid A and QS-21
Authors: Laird Renee M , Gariepy Christina L , Eggleston Heather , Shoemaker Nina M , Monteiro Mario A , Guerry Patricia , Beck Zoltan , Matyas Gary R , Poly Frédéric 
Published: January 2023

Abstract
Campylobacter jejuni is a major cause of infectious diarrhea worldwide. Increasing incidence of C. jejuni is attributed to new non-culture based detection methods and antibiotic resistance is unfortunately on the rise, necessitating development of interventions. Therapeutics development like vaccines have been hampered by lack of a small animal model that recapitulates campylobacteriosis symptoms. To better facilitate vaccine efficacy testing, we adapted a recently-published mouse C. jejuni infection model to adult mice fed a zinc-deficient diet and pre-treated with antibiotics prior to oral infection with C. jejuni strain 81–176. Non-vaccinated infected mice develop diarrhea, lose weight and show increased expression of fecal inflammatory markers indicating development of campylobacteriosis. We tested whether an 81–176 C. jejuni capsule conjugate vaccine delivered with a potent liposome adjuvant containing monophosphoryl lipid A and QS-21 known as ALFQ could protect mice against 81–176. Vaccinated mice developed high levels of anti-CPS IgG1 and IgG2b titers and serum bactericidal responses against 81–176. Vaccinated infected mice were protected against development of diarrhea, did not lose weight, and had significantly lower levels of fecal inflammatory marker expression. Importantly, vaccinated infected animals were protected against C. jejuni colonization indicating that parenteral vaccination with a conjugate vaccine plus the ALFQ adjuvant may provide protection against both C. jejuni disease and colonization. These promising results support further development of a multivalent C. jejuni conjugate vaccine platform delivered with potent adjuvant systems for use in human clinical studies.
Immunization with a subunit of housekeeping proteins provide partial protection against experimental necrotic enteritis in broiler chickens
Authors: Li Charles , Lillehoj Hyun , Yan Xianghe , Sun Zhifeng , Lu Mingmin , Yuan Baohong , Liu Liheng 
Published: January 2023

Abstract
Necrotic enteritis (NE) due to Clostridium perfringens (CP) infections is a prevalent enteric infectious disease accounting for $6 billion economical loss in global poultry industry. The increasing incidence of NE has been associated with the reduction and withdrawal of antibiotic growth promoters from animal feed during recent years. Therefore, the development of effective vaccines specific for NE assumes a priority for poultry industry. By far, no any effective vaccines are commercially available in broiler chickens. Our aim was to identify the potential CP proteins as vaccine targets for NE. We expressed 4 different recombinant CP proteins targeting 6 antigens: 3 major virulence-related toxins (alpha-toxin, NetB and TpeL), and 3 pilus subunit or enzymes (Collagen adhesion protein (Cna), Fructose-1,6-bisphosphate aldolase (FBA) and a Hypothetic protein (HP)), and their protection efficacies were evaluated with a severe Coccidiosis/NE challenge model using netB+tpeL+ CP strain. Young chicks were immunized twice subcutaneously with adjuvanted CP proteins on days 4, and 15. Prior to challenge, the chickens immunized with related antigens had much higher serum antibody titers for Cna and FBA/HP antigens than those with any of 3 toxin antigen-immunized groups. Following the challenge, the Cna-immunized group showed the least mortality and lowest lesion score among the individual antigen-vaccinated groups, while the pooled antigens-immunized group demonstrated no mortality against virulent challenges. The results indicate that the immunization with CP housekeeping protein, Cna, conferred better protection than other conventional virulence-related toxin proteins. Mucosal delivery system is being investigated next.
Intranasal vaccination induces complete protection against multidrug resistant A. baumannii pneumonia and sepsis
Authors: Shi Yun , Zeng Xi , Wang Ning , Guo Gang , Zou Quanming 
Published: January 2023

Abstract
In a WHO report released in Feb 2017, Acinetobacter baumannii has been list as top one of critical antibiotic-resistant “priority pathogens” which is in an urgent need for the new treatment. A. baumannii infections have become increasingly difficult to treat because most isolates are highly resistant to a wide range of antibiotics. With the absent of effective antibiotics, an effective vaccination regimen is urgently needed. We have established a pneumonia mouse model by non-invasive intratracheal instillation with A. baumannii and sepsis model by intraperitoneal injection of bacteria. Intranasal or intramascullar Vaccination both showed 100% protection against A. baumannii infection in pneumonia and sepsis model supported by reduced bacteria burderns, pathology, and reduced proinflammatory cytokine. Intranasal immunization also showed cross protection against different type clinical A. baumannii strains. A successful vaccine against A. baumannii will help us control its infection and overcome the development of multidrug resistance.
Systemic BCG Vaccination in “Dirty Mice” induces Protective Trained Immunity against TB
Authors: Kaufmann Eva , Khan Nargis , Robbins Clinton S , Barreiro Luis B , Divangahi Maziar 
Published: January 2023

Abstract
After a century of discovery of Bacille Calmette-Guerin (BCG), our understanding of its protective mechanism(s) against TB or other pathogens is very limited. We have recently demonstrated that systemic BCG vaccination (intravenously, iv) in specific pathogen-free (SPF) mice imprints hematopoietic stem cells (HSCs) to generate macrophages with a unique protective program against pulmonary M. tuberculosis (Mtb) infection. While this proof of concept study was an important step to determine how we can harness the power of innate (trained) immunity in vaccination against TB, the translation of this novel approach to humans is still unknown.
As SPF lab mice incompletely recapitulate the human immune system, additional pre-clinical models are necessary to evaluate the translational potential of systemic BCG vaccination. Thus, in the current study, we hypothesize that systemic BCG vaccination will generate protective HSC-mediated trained immunity against TB in microbe-exposed “dirty” mice whose immune landscape more closely replicates adult human traits.
To test this hypothesis, we have established a bedding transfer model from pet shop mice to SPF C57BL/6 mice. Age- and sex-matched dirty or SPF mice were then iv or subcutaneously vaccinated with BCG (1×106 CFU) or PBS (control). At 4 weeks post vaccination, we generated bone marrow derived macrophages and infected them with virulent Mtb (H37Rv; MOI 1). Interestingly, the protective signature of trained immunity was completely intact in BCG-iv vaccinated dirty mice.
Collectively, our results indicate that the protective imprinting of systemic BCG vaccination for generation of trained immunity is robust and independent of previous exposure of hosts to other microbes or pathogens.
Identifying mechanistic correlates of protection against Pseudomonas aeruginosa in an acute lung pneumonia model
Authors: Kilic Emel Sen , Blackwood Catherine B , Horspool Alexander M , Huckaby Annalisa B , Weaver Kelly , Malkowski Aaron , Witt William T , Bevere Justin R , Winters Michael T , Damron F. Heath , Barbier Mariette 
Published: January 2023

Abstract
Pseudomonas aeruginosa (Pa) is an opportunistic Gram-negative pathogen that can lead to life-threatening pulmonary infections. Several promising vaccine candidates against Pa evaluated in clinical trials. However, there is still no commercial vaccine available against this pathogen, in part due to a lack of clarity of protective correlates of vaccine–induced immunity. To elucidate correlates of protection against Pa, we used an intranasal whole–cell Pa vaccine adjuvanted with curdlan WCV in a murine vaccination and challenge model. Immunization with WCV significantly decreased the bacterial burden and lung edema after Pa challenge. We found that WCV immunization leads to a significant increase in Th17 cellular immune response and Pa–specific serum IgG and IgA titers compared to naive animals. To identify mechanistic correlates of protection, we performed anti–CD4, – CD8, and –CD20 antibody mediated depletions prior to vaccination and challenge. Depletion of these populations did not affect the response to challenge in naive animals. Interestingly, we observed that depletion of B cells but not CD8+ or CD4+ T cells during WCV priming resulted in loss of protection against Pa. Furthermore, passive immunization of WCV sera was sufficient to protect naive mice against Pa. Taken together, vaccine-mediated humoral immune response was the critical component of immunity against Pa in acute lung pneumonia model. This study suggests that adjuvants stimulating humoral immune response may be used to enhance the efficacy of vaccine candidates against Pa.
An AAV6-based multi-antigen vaccine for treatment of murine melanoma
Authors: Krotova Karina , Aslanidi George 
Published: January 2023

Abstract
We recently showed that a vaccine with optimized AAV6 vector generates a superior immune response against strong antigens (Ag) such as Ovalbumin. However, tumor-associated antigens (TAA) are typically non-mutated self-proteins with low immunogenicity. To increase vaccine efficacy and to reduce tumor evasion of immune attack, we developed a multivalent AAV vaccine that targets four previously characterized melanoma TAA: tyrosinase, premelanosome protein gp100, tyrosinase-related protein 1, and dopachrome tautomerase. The vaccine represents a combination of individual AAV-based vaccines specific to unique TAA. The strength of cytotoxic T cell response against each TAA was shown via IFNγ ELISPOT analysis of re-stimulated splenocytes from immunized mice. Additionally, we showed that vaccine-induced Ag-specific antibodies directed B16F10 melanoma cells to complement-dependent lysis. The vaccine’s therapeutic potential was analyzed in prevention and treatment of B16F10 mouse melanoma. The preventative vaccination significantly reduced the number of metastatic tumor nodules in lungs. Since B16F10 melanomas are immunologically resistant tumors, we combined vaccination with aPD-1 and aPD-L1 checkpoint inhibitors for treatment of established solid tumor. The combination of both vaccine and checkpoint inhibitors significantly delayed tumor growth and extended animal survival. In summary, our preliminary data suggest that a multivalent vaccine based on modified AAV6 vectors generates strong immune responses against endogenous self-proteins, and vaccination may have a therapeutic benefit against both metastatic and solid tumor development.
The efficacy and mechanism of CD020 on the induction of specific immune responses against HPV-related cancer
Authors: Song Ying-Chyi , Yen Hung-Rong 
Published: January 2023

Abstract
Virus infections may account for the development of several cancers, such as HPV16/18 are known to cause around 70% of cervical cancer cases. Until now, several immunotherapeutic approaches for virus-induced cancer are under development. Peptide-based vaccines have several advantages over conventional whole-protein vaccines in terms of purity, lot-to-lot consistency, production costs, and high antigenic specificity. However, the use of peptide antigens in vaccine development has been hampered by problems, such as weak immunogenicity coupled with a paucity of potent adjuvants. Specific T cell immune response is crucial for anti-tumor immunity. CD020 is a compound derived from the Chinese herbal medicine (CHM) of Hedyotis diffusa Willd. However, the efficacy and mechanism of CD020 on the induction of specific immune responses against cancer are still unclear. Therefore, we aimed to investigate whether CD020 can modulate specific T cell responses to apply for the development of a cancer vaccine. We have identified that CD020 could increase expression of maturation cytokines and activation markers of BM-DCs and induce specific T cell responses. Furthermore, in a murine TC-1 tumor-bearing model, we found that the CD020 could act as an adjuvant to induce cellular immune responses and anti-tumor effect in the peptide vaccine strategy. We suggested that immune-stimulator CD020 combined with cancer vaccine endows them with increased immunologic activity, which may be used to bypass the requirement for the conditional adjuvant. Further delineation of the mechanism may provide new clues for vaccination strategy.