bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal protection efficacy against influenza viruses by multi-subtype neuraminidase and M2 ectodomain virus-like particle vaccination in young and older adult mice
Authors: Kim Ki-Hye , Li Zhuo , Bhatnagar Noopur , Subbiah Jeeva , Park Bo Ryoung , Shin Chong Hyun , Kang Sang-Moo 
Published: January 2023

Abstract
Annual influenza vaccination is recommended to update the variable hemagglutinin antigens. [add more scientific justification for why NA + M2e immunity will be important?] Here, we first designed a virus-like particle (VLP) displaying consensus multi-neuraminidase (NA) subtypes (cN1, cN2, B cNA) and M2 ectodomain (M2e) tandem repeat (m-cNA-M2e VLP). Vaccination of mice with m-cNA-M2e VLP induced broad NA inhibition (NAI), M2e antibodies as well as interferon-gamma secreting T cell responses. Mice vaccinated with m-cNA-M2e VLP were protected against multi strains of different subtypes (H1N1, H5N1, H3N2, H9N2, H7N9) influenza A viruses containing substantial antigenic variations. From the T cell depletion and passive transfer experiments, we found that immunization of mice with m-cNA-M2e VLP induced cellular and humoral immune components contributing to broader cross protection. Also, surrogate effector assay indicated antibody-dependent cellular cytotoxicity as an additional protective immune contributor. Furthermore, comparable cross protection by m-cNA-M2e VLP vaccination was induced in aged mice. This study supports a novel strategy of developing a universal vaccine against influenza viruses potentially in both young and aged populations by inducing multi-NA subtype and M2e immunity with a single VLP entity.
Supported by grants from NIH/NIAID (AI093772, AI154656, AI147042)
The effects of metformin on influenza vaccination responses in healthy older adults
Authors: Martin Dominique Elizabeth , Cadar Andreia N , Haynes Laura , Kuchel George A , Bartley Jenna M 
Published: January 2023

Abstract
With aging, there is a progressive decline in the immune system leading to increased risk of infection and diminished vaccination responses. Concurrently, there are age-related changes to systemic and cellular metabolism. Influenza (flu) is a leading killer of older adults despite availability of a seasonal vaccine. Metabolic adjuvants may target metabolic deficits in immune cells and have potential to increase vaccination efficacy. Here we aimed to determine the effects of metformin, an FDA approved diabetes drug that targets AMPK and modulates cellular metabolism, on flu vaccination responses. In this study, healthy older adults (non-diabetic/non-prediabetic, age: 74.4±1.7 years) were randomized to metformin (n=8, 1500mg XR/daily) or placebo (n=7) treatment for 20 weeks. 10 weeks after the start of treatment, subjects were vaccinated with High Dose Flu Vaccine. Blood was obtained prior to treatment, prior to vaccination, and 1, 5, and 10 weeks post vaccination. To evaluate the effect of metformin treatment on vaccination responses, peripheral blood mononuclear cells (PBMCs), serum, and plasma were collected from each visit. Serum antibodies titers were quantified and PBMCs were stimulated with live flu virus to assess cell-mediated responses. Clear responses to vaccination were seen in T and B cell subsets via flow cytometry. There were trending increases in antibody fold changes with metformin, indicating a need to further explore the effects of metformin on humoral responses. Overall, metformin had no negative effects, but requires additional studies to determine if it has favorable effects on flu vaccine responses in healthy older adults.
Supported by American Federation for Aging Research (AFAR Diamond 18155, Bartley) and J. Bartley start up funds
Identification of conserved coronavirus epitopes targeted by antibodies after SARS-CoV-2 infection or vaccination
Authors: Bradley Todd , Geanes Eric , LeMaster Cas , Fraley Elizabeth R , Khanal Santosh , McLennan Rebecca , Grundberg Elin , Selvarangan Rangaraj 
Published: January 2023

Abstract
SARS-CoV-2 is a novel betacoronavirus that causes coronavirus disease 2019 and has resulted in millions of deaths worldwide. Novel coronavirus infections in humans have steadily become more common. Understanding antibody responses to SARS-CoV-2, and identifying conserved, cross-reactive epitopes among coronavirus strains could inform the design of vaccines and therapeutics with broad application. Here, we determined that individuals with previous SARS-CoV-2 infection or vaccinated with the Pfizer-BioNTech BNT162b2 vaccine produced antibody responses that cross-reacted with related betacoronaviruses. Moreover, we designed a peptide-conjugate vaccine with a conserved SARS-CoV-2 S2 spike epitope, immunized mice and determined cross-reactive antibody binding to SARS-CoV-2 and other related coronaviruses. This conserved spike epitope also shared sequence homology to proteins in commensal gut microbiota and antibodies targeting this region reacted with proteins in human fecal protein extracts. This indicated that the composition of the gut microbiota could prime immune responses in humans. Thus, SARS-CoV-2 conserved epitopes elicited cross-reactive immune responses to both related coronaviruses and host bacteria that could serve as future targets for broad coronavirus therapeutics and vaccines.
This work was supported through internal institutional funds from Children’s Mercy Research Institute and Children’s Mercy Kansas City.
Robust antibody responses in children after Pfizer vaccination
Authors: Gupta Sneh Lata , Anderson Evan J , Rostad Christina A , Suthar Mehul S , Wrammert Jens 
Published: January 2023

Abstract
SARS-CoV-2 is a devastating global pandemic which has resulted in mass loss of life. It is essential to vaccinate children to achieve herd immunity and prevent community transmission. In addition, the importance of vaccinating children is further illustrated by increasing COVID-19 cases among this age group and the associated Multisystem Inflammatory Syndrome in Children (MIS-C). Children possess a relatively naïve immune system compared to adults. With reopening of schools, relaxation of mask mandates and new emerging viral variants, it is imperative to better understand the magnitude and quality of vaccine induced responses in children, especially in terms of breadth of immunity against emerging viral variants.
In the current study we have assessed the humoral response after vaccination in children 11–17 years of age. We found robust responses in children, with Spike and RBD specific antibody titers that were significantly higher than adult vaccinees. In addition, these titers were also much higher than those seen in both convalescent hospitalized pediatric COVID and MIS-C cases. Compared to adults, the pediatric vaccinees showed a similar breadth against current viral variants. Finally, using a live neutralization assay we similarly found that children exhibited higher neutralization titers than adults and that the neutralization titers positively correlated with their RBD binding titers. Overall, our data show that vaccination induces more potent antibody responses in children as compared to adults, with similar breadth against emerging viral variants.
Durability of B and T cell responses against a spike protein of SARS-CoV2 elicited by mRNA vaccines
Authors: Hamilton Lauren Taylor , Koguchi Yoshinobu , Christie Tanisha , Shimada Takashi , Iwamoto Noriko , Fox Bernie , Redmond William L , Piening Brian D 
Published: January 2023

Abstract
The pandemic of SARS-CoV2 had resulted in over 266 million infections and over 5.2 million deaths throughout the world as of early-December 2021. Pfizer and Moderna mRNA vaccines were approved for Emergency Use Authorization by the US FDA. Even though 8.2 billion doses of vaccine have been administered, the world continues to see wide-spread SARS-CoV2 infection. Therefore, it is important to understand the durability of anti-SARS-CoV2 immune responses. Serum and PBMC samples were collected from vaccinated volunteers (N=40, Age 22–67, median age 41, Male/Female = 14/26, Moderna/Pfizer = 37/3) over 8 months (pre-vaccination baseline: TP1, 2 weeks-, 3 months-, and 8 months-post full vaccination: TP2, TP3, and TP4, respectively). First, we found robust induction of anti-S IgG and IgA for all subjects at TP2, which was higher than those from Covid-19 patients. Follow up samples (TP3 and TP4) showed steady decay of antibody levels over 8 months post-vaccination. Next, we evaluated memory B cell response using flow cytometry. We detected S-protein specific B cells by using flag-tagged S-protein. The frequency of S-protein specific B cells varied among donors and was weakly associated with the level of serum anti-S IgG antibody. Lastly, we assessed T cell responses. PBMCs were stimulated with an overlapping 15-mer peptide mix that covers the entire S-protein. Antigen-specific activation of T cells were detected based upon IFN-γ and TNF-α production. We found induction of robust CD4 T cell response at TP2 but a clear reduction at TP3. TP4 showed equivalent levels of T cell responses as TP3. Together, we found that B and T cell responses against the spike protein of SARS-CoV2 induced by mRNA vaccines are not durable.
This study was supported by funding from Shimadzu Corporation.
Oncolytic Viral Therapy Mediates its Effectiveness by Inducing and Enhancing CD4 cytotoxic T-cells
Authors: Grimes Jeffrey M , Murchison Charles , New James S , Crossman David , Markert James M , Leavenworth Jianmei Wu 
Published: January 2023

Abstract
Malignant glioma remains a fatal disease with a dismal survival rate. To address this urgent medical need, we pioneered the concept of engineered oncolytic viruses for cancer. Using the herpes simplex virus (HSV)-1 as an experimental virus, our published Phase I trials have demonstrated the safety and efficacy of such oHSV-based therapy for treating brain tumor patients. In searching for biomarkers for better responses to this therapy, our preclinical studies using intracranial glioma models and an oHSV secreting murine IL-12 (M002) revealed that a subset of CD4+ T-cells expressing the cytolytic signatures, including granzyme B, were increased in M002-treated mice compared to vehicle-treated controls. Correspondingly, CD4+ T-cells isolated from brain tumors of M002-treated mice killed tumor cells better than cells isolated from control tumors. However, the factors and temporal requirements that direct the development of this CD4 cytotoxic T-cell (CTL) subset are not fully understood. To address this question, we performed single-cell RNA sequencing analysis of CD4+ T-cells isolated from brain tumors of M002-treated and control mice. The results revealed a complex change of the CD4+ T-cell compartment with CD4 CTLs being induced from two different precursors. The first CTL subset was derived from T helper-1 (Th1) cells and retained Th1 gene signatures while expressing high levels of CTL associated molecules. The second CTL subset was a reprogrammed regulatory T-cell population capable of producing high levels of cytokines and granzymes. Both CD4 CTL subsets were more prominent in M002-treated mice, suggesting that M002 therapy could induce CD4 CTLs with specialized functionality, which may account for its improved outcome.
Supported by grants from DoD W81XH-18-1-0315 and UAB Start up Funds
Studies on Antibodies
Authors: Falk K. George , McGuire Grace , Valentine Eugenia , Whitney Elinor 
Published: January 2023

Abstract
Introduction. The preparation of dried antipneumococcus serum, tests of its protective action, and a number of its properties will be described in this paper.
The chemical nature of the active antipneumococcus material is unknown, whether this active material be considered to be a molecule, or a grouping in a complex protein or other molecule. The strength or potency of a preparation is determined at present by animal tests, agglutination and precipitation reactions. The animal tests used here were confined to mouse protection. As the significance of the experiments, such as the potency of a preparation after different treatments, would be determined by such mouse experiments, a critical discussion of this method of testing will first be given. It is evident that practically every treatment to which a labile material such as serum or plasma is subjected will modify its properties in one way or another.
Studies on Antibodies
Authors: Valentine Eugenia , McGuire Grace , Whitney Elinor , Falk K. George 
Published: January 2023

Abstract
Introduction. A method of drying antipneumococcus serums and antibody preparations, and some of the properties of these dried preparations were described in the preceding paper (1). The mouse protection, agglutination, and precipitin titers of dried antiserums when tested immediately and within two months after drying showed, in the majority of instances, a close correlation between the dried and untreated serums with respect to these antibody tests.
In this paper a more extended study of the correlation of agglutination, precipitin and mouse protection tests of dried antipneumococcus serums when stored at different temperatures and for different periods of time and the comparisons with the untreated materials will be described.
Experimental Methods and Results. Detailed results will be given for one antiserum, although similar results were obtained with several other antiserums. A dried powdered, antiserum was divided into two portions immediately after drying. One portion was kept in the ice-box and the other at room temperature.
Skin Reactions to the Colon Bacillus and Its Toxic Products
Authors: Steinberg Bernhard , Wiltsie Catherine Orth 
Published: January 2023

Summary and Conclusions
Normal persons give a positive reaction to intradermal injections of B. coli toxic filtrate and washed organisms. Children show a more marked reaction than adults. Patients with a long standing colon bacillus infection react slightly and a small percentage of the patients do not react at all. Negative reactions to the vaccine are more numerous than to the soluble toxic substance. Immunization with B. coli soluble toxic substance reduces but does not obliterate the reaction. Absence of B. coli agglutinins cannot be used as a criterion for absence of other neutralizing antibodies since the agglutinin titer was either nil or slight in persons with negative reactions.
Because normal persons give positive reactions and patients with long standing colon bacillus infection show negative or reduced reactions, the phenomenon is assumed by us to be one in which antibodies neutralize the colon bacillus toxic substances, both soluble and that derived from the bacterial bodies. Our work thus far does not justify either an acceptance or a refutation that thephenomenon may be of an allergic nature as suggested by some workers. It is further concluded that under the conditions of these experiments, the skin reaction for the determination of the presence of colon bacillus infection is of uncertain value.
Diphtheria Antibodies Transmitted from Mother to Child
Authors: Neill James M. , Gaspari Emidio L. , Richardson Lurline V. , Sugg John Y. 
Published: January 2023

Summary
Measurements were made of the diphtheria antibodies in the blood of a mother and baby during the eighteen months following the birth. Tests were made for antibodies of the antibacterial sort as well as for the antitoxin. The antibacterial antibodies were found in the serum of the baby over the period in which placentally transmitted antibodies could be expected to be retained, but owing to their passive origin they were absent in later bleedings. Control tests showed that the antibacterial antibodies were absent in the sera of babies whose mothers did not possess them. The data of the antitoxin tests owe their interest to the high degree of immunity of the mother and to the length of time over which the blood of both baby and mother was studied.
An Improved Diluent for Diphtheria Toxin in the Schick Test
Authors: White Benjamin , Bunney W. E. , Malcolm Wilbur G. 
Published: January 2023

Summary
An improved method is described for preparing diphtheria toxin ready diluted for the Schick test. Diphtheria toxin diluted to Schick strength (1/5 m.l.d. per cubic centimeter) with an aqueous solution of Witte peptone 0.25 per cent, sodium chloride 0.85 per cent and phenol 0.5 per cent and passed through a Berkefeld filter retains its toxicity even after ninety-six hours' incubation at 37.5°C. The reactions following the injection into human beings of this ready-diluted toxin and of toxin freshly diluted, as in the previous Schick outfits, are entirely comparable. The use of 0.25 per cent Witte peptone is preferable to 2 per cent Difco-Proteose peptone because of its failure to produce early or diffuse reactions.
Lung Resident Memory T Cells Activated by Oral Vaccination Afford Comprehensive Protection against Pneumonic Yersinia pestis Infection
Authors: Singh Amit K , Majumder Saugata , Wang Xiuran , Song Renjie , Sun Wei 
Published: January 2023

Abstract
A growing body of evidence has shown that resident memory T (TRM) cells formed in tissue after mucosal infection or vaccination are crucial for counteracting reinfection by pathogens. However, whether lung TRM cells activated by oral immunization with Yptb1(pYA5199) play a protective role against pneumonic plague remains unclear. In this study, we demonstrated that lung CD4+ and CD8+ TRM cells significantly accumulated in the lungs of orally Yptb1(pYA5199)-vaccinated mice and dramatically expanded with elevated IL-17A, IFN-γ, and/or TNF-α production after pulmonary Yersinia pestis infection and afforded significant protection. Short-term or long-term treatment of immunized mice with FTY720 did not affect lung TRM cell formation and expansion or protection against pneumonic plague. Moreover, the intratracheal transfer of both lung CD4+ and CD8+ TRM cells conferred comprehensive protection against pneumonic plague in naive recipient mice. Lung TRM cell–mediated protection was dramatically abolished by the neutralization of both IFN-γ and IL-17A. Our findings reveal that lung TRM cells can be activated via oral Yptb1(pYA5199) vaccination, and that IL-17A and IFN-γ production play an essential role in adaptive immunity against pulmonary Y. pestis infection. This study highlights an important new target for developing an effective pneumonic plague vaccine.
Heredity of the Agglutinogens M and N of Landsteiner and Levine
Authors: Wiener Alexander S. , Rothberg Sidney , Fox S. A. 
Published: January 2023

Summary
The bloods of 461 mothers with 495 children were examined for the agglutinogens M and N of Landsteiner and Levine. Not once were the combinations, M+N- mother with M-N+ child, or M-N+ mother with M+N- child found. The results fully confirm the theory of Landsteiner and Levine. The medicolegal application of the agglutinogens M and N is fully justified at present.
The Agglutinin Response to Typhoid-Paratyphoid Vaccination
Authors: Mudd Stuart 
Published: January 2023

Summary
Recent claims that prophylactic vaccination against typhoid and paratyphoid fever is not effective because of the absence of somatic antibodies in the sera of vaccinated persons have not been substantiated; somatic antibodies could be detected with proper reagents after administration of a proper vaccine. A vaccine which failed to prevent small outbreaks of typhoid and paratyphoid B infection in a state hospital was found to be deficient in production of somatic agglutinins and its bacterial count was far below specifications. A convenient detector of H agglutination, namely chloroform-treated bacilli, is described.
Some Factors Influencing the Rate of Thermal Destruction of the Tetanus Antitoxin of Antitetanic Horse Plasma at 60° to 66°C.
Authors: Gerlough Tillman D. , White Woodford 
Published: January 2023

Summary
Data are presented to show the influence of ammonium sulphate, phenol and pH on the heat destruction at 60° to 66°C. of tetanus antitoxin of antitetanic horse plasma. The results may be summarized as follows: Addition of neutral salts increased the rate of destruction of tetanus antitoxin up to an ionic strength of 0.6 to 0.9 where a maximum is reached. With further addition of salt the rate decreased.The pH of maximum stability is at or near neutrality.Phenol increases markedly the rate of destruction of tetanus antitoxin. Its accelerating action is approximately proportional to the square of the phenol concentration.Between 60° and 66°C. an increase in temperature of 1°C. increases the rate of destruction of tetanus antitoxin 1.85 times.
Schick Reactions and Serum Antitoxin Titrations on Children Injected with Diphtheria Formol Toxoid
Authors: Leach Charles N. , Pöch Georg 
Published: January 2023

Abstract
The customary method of determining the effectiveness of diphtheria immunization by various antigens is the well known Schick skin test. This has been considered an indirect means of estimating a certain amount of antitoxin in the blood of individuals before and after injection with the antigen employed. Schick and Michaels (1913) stated that a negative Schick test should indicate an amount of antitoxin present in the blood serum of the subject under investigation not below 0.03 of a unit per cubic centimeter of serum (0.02 units per cubic centimeter of blood). This lower level of protection was later placed at 0.005 unit per cubic centimeter of serum (Schick, von Gröer, and Kassowitz, 1924) and in recent years 0.01 unit per cubic centimeter of serum has been considered sufficient to protect against diphtheria (Dudley, Surg. Capt. S. F., 1934). The so-called “Schick level” is now placed between 0.03 and 0.01 units.
Neutralization of the Bacteriophage
Authors: Clifton C. E. , Mueller Elizabeth , Rogers W. 
Published: January 2023

Summary and Conclusions
The time required for an anticoliphage to lyse an actively growing culture of Esch. coli is proportional to the initial concentration of the phage. Other conditions being constant, the concentration of phage in different samples can be determined by noting the relative length of time required for the reduction of a constant initial concentration of bacteria to an arbitrary turbidity endpoint. The time required for a given initial concentration of phage to reduce the concentration of bacteria to this arbitrary end-point is increased in the presence of an antilytic serum. Quantitative measurements, under the dynamic conditions of these experiments, indicate that the neutralization of phage over a wide range of concentrations of phage and of antiserum, goes almost to completion within a few minutes. Observations are presented which suggest that the preliminary union between phage and antiphage is an adsorption process.
Procedure and Apparatus for Preservation in “Lyophile” form of Serum and Other Biological Substances
Authors: Flosdorf Earl W. , Mudd Stuart 
Published: January 2023

Summary
Procedure and apparatus for the preservation of biological products in lyophile form have been described in detail. The method is one of rapid freezing and rapid dehydration from the frozen state. The product is vacuum sealed in the final container in which it is to be stored and distributed.
The apparatus is simple in operation. Models have been described for use in research laboratories, for board of health and hospital work and for industrial scale production.
Normal and convalescent human sera, animal antisera and complement, miscellaneous proteins, enzymes, viruses, bacteria and other materials have been preserved. Complement may be preserved without detectable deterioration for at least ten months, and indications are that many types of antisera may probably be preserved unaltered for an indeterminate number of years.