bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in B cell frequencies and antibody responses following influenza vaccination in healthcare workers during the 2019–2020 season
Authors: Park Han-Sol , Kuo Helen , Liu Hsuan , Fenstermacher Katherine , Shapiro Janna , Jedlicka Anne , Dhakal Santosh , Ursin Rebecca , Wilson Jo , Shea Patrick , Morgan Rosemary , Gearhart Patricia J , Rothman Richard , Pekosz Andrew , Klein Sabra L 
Published: January 2023

Abstract
Annual influenza vaccination for healthcare workers (HCWs) is required at Johns Hopkins to reduce influenza spread in healthcare facilities. We conducted a clinical study to evaluate sex differences in virus-specific antibody-producing B cells (i.e., plasmablasts) following receipt of the seasonal influenza vaccine in a highly vaccinated population of healthcare workers. To understand sex differences in immune responses to the influenza vaccine in the HCWs, 83 participants consented to blood draws at baseline and 75 participants returned for the 7- and 28-days post-vaccination survey and blood draw. Participants received their annual quadrivalent influenza vaccine (QIV). Influenza A specific plasmablasts were quantified at baseline and day 7 post-vaccination. Males had a significantly greater percentage of influenza-specific plasmablasts than females after vaccination (p&lt;0.0003) Plasma collected at baseline and at day 28 post-vaccination was used to measure neutralizing antibody (nAb) titers against H1N1 and H3N2 vaccine viruses. Neutralizing antibody responses against either the H1N1 and H3N2 viruses increase after vaccination to the same degree in both males and females. The proportion of plasmablasts at day 7 was significantly associated with the vaccine-induced fold rise in nAb. This relationship differed by sex, whereby for a given proportion of plasmablasts, females tended to mount a greater fold-rise in nAb than males. These data suggest that despite having potentially fewer plasmablasts after vaccination, females mount an antiviral antibody response to the influenza vaccine viruses equivalent to males. Identification of transcriptional differences in plasmablasts from male and female HCWs is ongoing.
Estradiol replacement improves vaccine-induced antibody responses and protection against influenza in aged female mice
Authors: Mueller Alice R L , Dhakal Santosh , Caputo Christopher , Seddu Kumba , Klein Sabra L 
Published: January 2023

Abstract
Adult female mice generate greater vaccine-induced immunity and protection than their male counterparts, but this female advantage is lost with age. We hypothesized that treatment of aged female mice with exogenous estradiol would improve vaccine-induced antibody responses and protection from both pulmonary infection and disease after live influenza virus challenge. To investigate this, adult (2–3 months old) and aged (17–18 months old) female C57BL/6 mice were implanted with either empty (placebo) capsules or capsules loaded with 17β-estradiol (E2) hormone, and then vaccinated with mouse-adapted A/California/04/09 (ma2009 H1N1) vaccine. Total IgG and neutralizing antibody titers (nAb) were quantified using blood samples collected post vaccination. &gt;1 month post vaccination, mice were challenged intranasally with ma2009 H1N1 drift variant virus. A subset of mice was euthanized at 3 days post challenge to collect lungs and measure infectious virus titer. Another subset was followed for 14 days to measure changes in body mass as a measure of disease severity. We found that aged female mice treated with E2 produced significantly greater IgG and nAb responses compared to placebo-treated aged females, and the responses of E2-treated aged females were comparable to the antibody responses generated in adult females. Treatment with E2 also reduced morbidity, but not pulmonary virus titers, following live virus challenge. Our data suggest that estrogen replacement in aged female mice improves their humoral immune response to influenza vaccination and protects them from severe disease.
Supported by U54AG062333
Preventing neonatal herpes: Protection after maternal mRNA-lipid nanoparticle vaccination equals or exceeds that from prior maternal genital infection in murine models
Authors: Desmond Angela , LaTourette Philip C , Awasthi Sita , Egan Kevin P , Hook Lauren M , Brice Angela K , Lubinski John M , Naughton Alexis M , Fowler Bernard , Beattie Mitchell , Pardi Norbert , Cohen Gary H , Weissman Drew , Friedman Harvey M 
Published: January 2023

Abstract
Neonates are vulnerable to poor outcomes from herpes simplex virus (HSV), but maternal infection eliciting non-sterilizing immunity prior to delivery provides some protection. We are therefore pursuing birthing parent vaccination with nucleoside-modified mRNA-lipid nanoparticles (mRNA-LNPs) to prevent neonatal herpes. Our trivalent vaccine encodes HSV type 2 (HSV-2) proteins involved in attachment and immune evasion (gC2, gD2, and gE2). We have shown that this vaccine protects against genital HSV and neonatal HSV-2 in mice. Here, we tested how well murine dam vaccination prior to pregnancy protects pups against HSV type 1 (HSV-1) challenge compared to prior maternal intravaginal HSV-1 infection. Dams were immunized intramuscularly with the HSV-2 trivalent mRNA-LNP vaccine or a control immunogen (PolyC RNA-LNP), or were infected intravaginally with HSV-1 (HSV-1 ivag). Pups were challenged intranasally with HSV-1 on the 3rd day of life. Pups born to dams previously immunized or infected survived through 28 days (mRNA 95% vs. HSV-1 ivag 96%, N.S.; vs. PolyC 13%, p&lt;0.0001). Likewise, they were protected from HSV-1 dissemination to the brain, lung, liver, spleen, and kidney by plaque assay (mRNA 2/45 organs affected vs. HSV-1 ivag 6/20, p=0.0083; vs. PolyC 69/80, p&lt;0.0001). Additionally, fewer organs showed necrosis by histopathology of brain, lung, and liver, though not statistically significant, and fewer mRNA and HSV-1 ivag pups had detectable HSV-1 DNA in the trigeminal ganglia by qPCR (mRNA 6/30 vs. HSV-1 ivag 7/26, N.S.; vs. PolyC 17/18, p&lt;0.0001). These studies demonstrate that the mRNA vaccine provides comparable to improved protection against neonatal HSV-1 challenge versus prior maternal HSV-1 intravaginal infection.
AD was supported by NIH NIAID T32 AI118684. HMF, SA, GHC, and DW were supported by NIH NIAID R01 AI139618 and an unrestricted grant from BioNTech SE. KPE was supported by NIH T32 NS007180. The funders had no input or influence on the content of this abstract.
The immunologic effects of different adjuvants on enhancing homologous and cross-protection by influenza virus vaccination in young and aged mice
Authors: Bhatnagar Noopur , Kim Ki-Hye , Subbiah Jeeva , Park Bo Ryoung , Ko Eun-Ju , Wang Pengfei , Kang Sang-Moo 
Published: January 2023

Abstract
Seasonal vaccination is ineffective in the elderly population and in conferring cross-protection against antigenically different influenza viruses. Therefore, the cross-protective efficacy of influenza vaccines needs to be improved. Here, we compared the effects of different adjuvants (QS-21+MPL, CpG+MPL, BCG CWS, Saponin VSA-1, Quil-A, and Alum) on enhancing the immunogenicity and homologous and cross-protection by influenza vaccination in mice. QS-21+MPL adjuvant was most effective in inducing Th1 T cell, cross-reactive IgG, and hemagglutination inhibiting antibody responses to vaccination. QS-21+MPL and CpG+MPL adjuvants exhibited high potency by preventing weight loss and reducing viral loads and conferring enhanced homologous and cross-protection in young and aged mice. BCG cell-wall skeleton (CWS) displayed lower adjuvant efficacy in inducing Th1 IgG responses and conferring cross-protection. VSA-1 (an analog of licensed adjuvant QS-21) exhibited adjuvant effects on enhancing the protective efficacy against homologous and heterosubtypic viruses comparable to QS-21. Saponin Quil-A exhibited adjuvant effects in CD4-deficient mice suggesting a CD4-independent adjuvant mechanism, in contrast to CpG that requires intact CD4 T cells. The findings suggest that QS-21+MPL, CpG+MPL, and VSA-1 exhibit desirable adjuvant properties on enhancing cross-protective humoral and cellular immunity to vaccination, with a unique pattern of innate immune responses, contributing to improved homologous and heterosubtypic protection. This study has significance in better understanding the effects of potent adjuvants on enhancing homologous and cross-protection to influenza vaccination in young and older adults.
This study was supported by NIH/NIAID grants AI093772 (S.M.K.), AI154656 (S.M.K), and AI147042 (S.M.K).
Robust efficacy and long-lasting humoral immunity induced by a respiratory syncytial virus prefusion F-based nanoparticle vaccine in genetically diverse animal models
Authors: Stephens Laura , Ross Kathleen A , McLellan Jason S , Narasimhan Balaji , Varga Steven M 
Published: January 2023

Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children, accounting for 7% of deaths in those less than one year of age. Despite multiple exposures to RSV throughout life, natural infection affords only partial protection and there is currently no licensed vaccine against RSV. We developed a vaccine candidate, RSVNanoVax, composed of polyanhydride nanoparticles encapsulating the RSV prefusion F protein and a CpG1668 adjuvant. To assess the efficacy of RSVNanoVax we utilized two model systems with increased genetic variability, Swiss Webster mice and the cotton rat. Following an intranasal prime-boost vaccination with RSVNanoVax, Swiss Webster mice exhibited robust titers of RSV F-directed IgG antibodies in both the serum and lung tissue that were sustained out to at least 1-year post-vaccination. RSV F-directed IgA was also induced within the lung tissue and nasal passages, suggesting that RSVNanoVax stimulates long-lasting systemic and mucosal antibody responses in outbred mice. Serum antibodies maintained robust neutralizing activity against both RSV A and B virus strains. Following RSV challenge, vaccinated mice exhibited complete viral clearance in the lungs as early as day 2 post-infection. Further studies performed in cotton rats demonstrated that RSVNanoVax conferred protection from both viral replication in the lungs as well as RSV-induced pulmonary immunopathology following viral challenge. Vaccinated cotton rats also exhibited robust titers of RSV F-directed serum antibodies with neutralizing capacity. Overall, RSVNanoVax represents a promising RSV vaccine candidate capable of providing long-term protection and immunity in genetically diverse populations.
Supported by grants from NIH (R01 AI124093, T32 CA078586, T32 AI007485)
Conserved-region MVA vaccines can shift HIV T cell immunodominance in PWH on ART - the M&M Study
Authors: Xu Yinyan , Samir Shahryat , Weideman Ann Marie K , Kallon Sallay , Conrad Shayla , Shaw Fiona , Warren Joanna , Fernandez Maria Abad , Fox Lawrence , Margolis David M , Hudgens Michael G , Hanke Tomas , Kuruc JoAnn , Gay Cindy , Goonetilleke Nilu 
Published: January 2023

Abstract
CD8+ T cell immunity is essential to the control of HIV viremia. We examined the safety and immunogenicity of MVA-vectored vaccines expressing highly conserved HIV regions in a first-in-man Phase I study in people living with HIV on ART. Participants received a single intramuscular dose of MVA.tHIVconsv3 (M3), MVA.tHIVconsv4 (M4), combined M3+M4 or saline in a 7:7:7:3 ratio. M3 and M4 span the same 6 HIV regions but differ by approximately 10% of amino acids; a design to increase vaccine coverage of circulating HIV variants. We employed ex vivo IFN-g ELISpot assays to measure changes in HIV-specific T cell magnitude and breadth to M3 and/or M4 immunogens following vaccination. We also examined whether M3, M4 or M3+M4 vaccination increased the ability of CD8+ T cells inhibit HIV in vitro replication.
The M&M study is fully enrolled but presently is blinded. Analysis of blinded data show that vaccination was safe and well tolerated. Vaccination induced strong increases in the T cell response to M3, M4 vaccine immunogens producing a 2- to 18-fold increase in magnitude in 16/20 participants tested to date. M3/M4-specific T cell breadth also increased across participants. Vaccine-associated T cell responses mostly remained elevated (&gt;2-fold increase) for at least 70 days post-vaccination visit. Vaccination was also associated with clear and sustained increases in in vitro virus inhibition. The percentage of the total HIV T cell response targeting conserved HIV regions in participants increased on average from 40 to 60% post-vaccination, suggesting M3/M4/M3+4 vaccination successfully produced a sustained shift in T cell immunodominance. Unblinded data will be presented at this meeting.
Supported by U01AI131310
Immunogenicity of a germline-targeting nanoparticle in knock-in mice expressing human B cell receptors of the HIV gp41 neutralizing antibody, DH511
Authors: Cain Derek Wilson , Tian Ming , Schiffner Torben , Rantalainen Kimmo , Saunders Kevin O , Wiehe Kevin , Watts Brian , Ward Andrew , Ofek Gilad , Alt Frederick W , Haynes Barton F , Schief William R , Alam S Munir 
Published: January 2023

Abstract
The Membrane Proximal External Region (MPER) of HIV Envelope represents a key target for vaccine development due to high neutralization breadth and potency of MPER-specific broadly neutralizing antibodies (bnAbs). However, neutralizing antibody responses to MPER epitopes are restricted by tolerance control and the MPER epitope is absent from many HIV immunogens under clinical investigation. Using computational design and yeast display, a candidate germline-targeting (GT5) immunogen was developed that bound strongly to the inferred human unmutated common ancestor (UCA) of the distal MPER bnAb DH511, as well as to several human DH511-like potential precursor antibodies. We studied the immunogenicity of a multimeric nanoparticle of the GT5 immunogen in a knock-in mouse line expressing human DH511.UCA B cell receptors (BCRs). Naïve DH511.UCA knock-in mice exhibited a reduction in overall B cell numbers, and DH511.UCA-bearing B cells expressed low levels of surface IgM and IgD, suggesting that DH511.UCA expression is subject to immune tolerance control. Nonetheless, following immunization with GT5 nanoparticles mixed with a saponin/monophosphoryl lipid A adjuvant, knock-in mice mounted robust anti-GT5 humoral responses, including anti-GT5 IgG in serum and GT5-specific germinal center B cells and T follicular helper cells in lymphoid tissues. Sequencing analysis of IgG+ GT5-specific B cells revealed improbable mutations in knock-in immunoglobulin genes of DH511.UCA. These studies will guide further optimization of immunogens with potential to select for development of bnAbs against MPER epitopes.
Supported by a grant from NIH (P01-AI138211)
Application of M-cell targeting ligand Co4B enhances Ag-specific mucosal and systemic immunity and protection against MERS-CoV infection after intranasal immunization
Authors: Jang Yong-Suk , Yang Ye Lin , Kim Ju , Cho Byeol-Hee 
Published: January 2023

Abstract
Middle East respiratory syndrome is associated with severe pneumonia and poses a global public health threat. Authorized vaccines against the causative agent of MERS-CoV are urgently needed. In order to optimize the efficacy of recombinant vaccines, adjuvants should be required. Therefore, we previously identified a ligand Co4B as an adjuvant to enhance Ag delivery to the nasal mucosa immune compartment and promote Ag-specific mucosal and systemic immune responses via intranasal administration against A. pleuropneumoniae infection in a murine model. Based on the pathogenesis of MERS-CoV which infects host following respiratory route; thus, we generated a recombinant protein conjugated with Co4B to the MERS-CoV spike protein receptor-binding domain (S-RBD) to develop mucosal subunit vaccine candidate. Ag-specific mucosal IgA and systemic IgG antibody responses, together with virus-neutralizing capacities, were highly elicited in C57BL/6 and human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice intranasally immunized with Co4B-conjugated S-RBD compared to those immunized with originally S-RBD. Ag-specific T cell-mediated immunity was also induced in the spleen and lungs of mice intranasally immunized with Co4B-conjugated S-RBD. Intranasal immunization of hDPP4-Tg mice with Co4B-conjugated S-RBD prominently reduced immune cell infiltration into the tissues of virus-challenged mice. Finally, Co4B-conjugated S-RBD-immunized mice demonstrated were improved protection against infection, more likely to survive, and exhibited less body weight loss. Collectively, our results suggest that Co4B-conjugated S-RBD could be used as an improved subunit vaccine candidate against MERS-CoV infection.
This work was supported by the Ministry of Science and ICT No. 2020K1A4A7A02095058 and the NRF funded by the Ministry of Education No. 2019R1I1A3A01062224. Ms. Y. L. Yang and Ms. B.-H. Cho were supported by the BK21 FOUR program of the Department of Bioactive Material Sciences.
Sex differences in the pre-treatment cytokine signatures associated with response and survival in B cell lymphoma patients treated with anti-CD19 CAR T-cell therapy
Authors: Gupta Neetu , Patel Manishkumar S , Jalota Akansha , Mian Agrima , Bazeley Peter , Hunter Sara A , Hill Brian T 
Published: January 2023

Abstract
Many autoimmune diseases, and in some instances, immune response to infections exhibit gender bias. However, it is not known if gender influences the response of lymphoma patients to anti-CD19 CAR T-cell therapy. To address this, we profiled 51 pre-treatment serum cytokines and chemokines to identify those that were differentially associated with response and survival in male vs. female relapsed/refractory large B-cell lymphoma (R/R LBCL) patients treated with Axicabtagene ciloleucel. Male non-responders (stable/progressive disease) had significantly higher baseline levels of IL-6, IL-8, IL-1RA, MIP-1α, GM-CSF and CRP compared to responders (complete/partial response). Higher levels of IL-6, IL-8, IL-27, and CRP were significantly associated with poor overall survival (OS), and IL-6, IL-8, MIP-1β, and CRP with poor progression-free survival (PFS) in male but not female patients. Baseline metabolic tumor volume (MTV) and lactate dehydrogenase (LDH) levels were also significantly higher in male patients with poor OS and PFS. Finally, baseline IL-8 and CRP were significantly correlated with baseline MTV and LDH levels in male but not female patients. Taken together, elevated baseline levels of IL-8, IL-6, CRP with high pretreatment tumor burden in male non-responder R/R LBCL patients point to an immunosuppressive tumor microenvironment that can potentially hinder anti-tumor activity prior to treatment and CAR T-cell expansion upon treatment in these patients, and result in poor outcomes.
Effect of Herbal Detoxification and Reverse Diet Treatment on the Mortality Rate of CAD Patients
Authors: Sane Rohit , Mandole Rahul , Amin Gurudatta , Ghadigaonkar Pravin , Dawkhar Suhas 
Published: January 2023

Background:
Coronary Artery Disease (CAD) has metabolic disorders at its core etiology. Ayurvedic-based Panchkarma treatment has previously been reported to have reversed CAD-related conditions and improved the quality of life post-treatment.

Objectives:
The current study was designed to determine the effectiveness of Ayurvedic-based Panchkarma treatment as assessed by the mortality and rehospitalization rate.

Methods:
This was a multicenter cohort study carried out between August 2017 and August 2020 in India. The study enrolled known CAD patients (stable at rest). The study therapy included a three-step Panchkarma treatment and a low-calorie high-protein diet kit for 12 months and was monitored for up to 36 months. The hazard ratios for different risk factors including – age, body mass index (BMI), weight, diabetic status, and blood pressure were calculated using the Cox proportional hazards model and the actual number of deaths that occurred over the study period (24 months and 36 months) were recorded.

Results:
The study included 572 known CAD patients (78.67% of males and 21.33% of females) within the age group of 60.22 ± 10.89 years (mean ± standard deviation). Complete compliance to study therapy was recorded whereas ~15%–25% of patients were unable to follow the dietary modifications. The overall mortality rate was found to be 5.07%. BMI, weight, diabetes, and blood pressure were modified during the treatment which may have led low mortality rate. Statistically, age was the only risk factor that showed significance in determining overall survival. The total number of cases of rehospitalization during the study period was 52 (9.09%) patients.

Conclusion:
Our study concluded that the Panchakarma-based treatment is beneficial in reducing risk factors such as BMI, diabetes, and blood pressure in known CAD patients, thus lowering the mortality and rehospitalization rate posttreatment.
Molecular characterization and frequency of transforming growth factor beta 1 gene polymorphism and its relation to bone complications in Egyptian patients with β-thalassemia
Authors: Elgawhary Somaya M. , Mohammed Manal N. , Ahmed Heba M. , Elamir Ahmed M. , Abdelaziz Hossam M. 
Published: January 2023

Objective
The objective of this study was to determine the frequency of transforming growth factor beta 1 (TGFβ1) C-509T gene polymorphism and its relation to bone complications in patients with β-thalassemia major in Egypt.

Background
Osteoporosis is the most prevalent bone complication in patients with β-thalassemia major despite regular blood transfusions and iron chelation therapy. It is characterized by low bone mineral density (BMD) resulting in reduced bone strength and increased risk of fractures. Genetic factors play an important role in the determination of BMD. The TGFβ1 gene, which encodes TGFβ1, is a strong candidate for susceptibility to osteoporosis, and several studies have reported associations between BMD and different polymorphisms of TGFβ1, although these studies have yielded conflicting results.

Study design and methods
Single nucleotide polymorphism in the TGFβ1 gene promoter (C-509T) was investigated in 100 regularly treated Egyptian children with β-thalassemia major by PCR/RFLP genotyping. BMD was measured by dual-energy radiograph absorptiometry and expressed as Z score.

Results
The frequency of TGFβ1 gene polymorphism C-509T genotypes in all studied patients was 6% for homozygous CC, 85% for heterozygous CT, and 9% for homozygous TT. C allele frequency was 48.5%, whereas T allele frequency was 51.5%. BMD Z score was significantly higher in TT genotype compared with CC genotype, with P value less than 0.05. Patients were grouped on the basis of BMD Z score: 51 (51%) patients with BMD deficit (Z score <−1) and 49 (49%) with normal BMD (Z score ≥−1). TGFβ1 gene polymorphism C-509T genotypes were distributed differently between the two groups; the TT genotype frequency was lower in patients with BMD deficit (P<0.05).

Conclusion
TGFB1 gene polymorphism C-509T is associated with BMD and genetic susceptibility to osteoporosis and may play a role in the pathogenesis and modification of bone complication in β-thalassemia major. BMD deficit is common in Egyptian children with β-thalassemia major. Analysis of this polymorphism at an early age could help in identification of thalassemic children at risk of osteoporosis and early management. However, large-scale studies are required to confirm these findings.