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Results: 1 to 10 of 81

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Operationalizing outcome measures of human papillomavirus vaccination among adolescents.
Odoh C, Sanderson M, Williams EA, Hull PC
(2018) Public Health 159: 129-132
MeSH Terms: Adolescent, Cross-Sectional Studies, Female, Health Care Surveys, Humans, Immunization Schedule, Male, Outcome Assessment, Health Care, Papillomavirus Infections, Papillomavirus Vaccines, Time Factors, Vaccination
Show Abstract · Added July 11, 2019
OBJECTIVES - When examining vaccination coverage, researchers must make decisions about how to define outcome measures based on many factors, including the timing of doses. Different operationalizations of the same outcome can often lead to different findings and can affect the ability to make comparisons across studies. This methodological article aimed to illustrate the implications of two options for operationalizing human papillomavirus (HPV) vaccination based on timing: initiation of the first dose at any age vs before the 13th birthday (on time).
STUDY DESIGN - Cross-sectional observational design.
METHODS - The 2014 National Immunization Survey for Teens (N = 16,439 adolescents aged 13-17 years) was analyzed using multivariate logistic regression for each outcome measure and effect modification by gender.
RESULTS - Age was positively associated with initiation at any age but negatively associated with on-time initiation. Gender modified the effect of race/ethnicity for both measures of initiation, but the pattern across groups was different for the two outcomes. Gender modified the effect of provider recommendation for initiation at any age, while gender modified the effects of age and region for on-time initiation.
CONCLUSION - Decisions of how to operationalize outcomes of HPV vaccine initiation among adolescents can lead to different conclusions about the role of age and gender differences for several predictive variables. To inform the development of public health efforts that promote on-time HPV vaccination among male and female adolescents, researchers should consider the importance of dose timing when operationalizing outcome measures. We recommend including on-time receipt of the HPV vaccine as an outcome measure.
Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
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12 MeSH Terms
Countrywide demonstration of adult protection derived from infant immunisation.
Grijalva CG
(2018) Thorax 73: 208-209
MeSH Terms: Adult, Humans, Immunization, Infant, Vaccination
Added July 27, 2018
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5 MeSH Terms
Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.
Saunders KO, Verkoczy LK, Jiang C, Zhang J, Parks R, Chen H, Housman M, Bouton-Verville H, Shen X, Trama AM, Scearce R, Sutherland L, Santra S, Newman A, Eaton A, Xu K, Georgiev IS, Joyce MG, Tomaras GD, Bonsignori M, Reed SG, Salazar A, Mascola JR, Moody MA, Cain DW, Centlivre M, Zurawski S, Zurawski G, Erickson HP, Kwong PD, Alam SM, Levy Y, Montefiori DC, Haynes BF
(2017) Cell Rep 21: 3681-3690
MeSH Terms: AIDS Vaccines, Amino Acid Sequence, Animals, Antibodies, Neutralizing, Disease Models, Animal, Epitopes, HIV Antibodies, HIV-1, Immunization, Macaca mulatta, Mice, Polysaccharides, Protein Multimerization, Rabbits, env Gene Products, Human Immunodeficiency Virus
Show Abstract · Added March 14, 2018
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VDJ) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs V chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define V replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.
Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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15 MeSH Terms
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.
Zhou T, Doria-Rose NA, Cheng C, Stewart-Jones GBE, Chuang GY, Chambers M, Druz A, Geng H, McKee K, Kwon YD, O'Dell S, Sastry M, Schmidt SD, Xu K, Chen L, Chen RE, Louder MK, Pancera M, Wanninger TG, Zhang B, Zheng A, Farney SK, Foulds KE, Georgiev IS, Joyce MG, Lemmin T, Narpala S, Rawi R, Soto C, Todd JP, Shen CH, Tsybovsky Y, Yang Y, Zhao P, Haynes BF, Stamatatos L, Tiemeyer M, Wells L, Scorpio DG, Shapiro L, McDermott AB, Mascola JR, Kwong PD
(2017) Cell Rep 19: 719-732
MeSH Terms: Animals, Antibodies, Neutralizing, Antibody Specificity, Binding Sites, CD4 Antigens, Crystallography, X-Ray, Epitopes, Glycosylation, Guinea Pigs, HIV Antibodies, HIV-1, Humans, Immunization, Macaca mulatta, Molecular Dynamics Simulation, Polysaccharides, Protein Structure, Quaternary, env Gene Products, Human Immunodeficiency Virus
Show Abstract · Added May 3, 2017
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.
Published by Elsevier Inc.
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18 MeSH Terms
Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine.
Li B, Siuta M, Bright V, Koktysh D, Matlock BK, Dumas ME, Zhu M, Holt A, Stec D, Deng S, Savage PB, Joyce S, Pham W
(2016) Int J Nanomedicine 11: 6103-6121
MeSH Terms: Adjuvants, Immunologic, Administration, Intranasal, Animals, Cell Death, Cell Proliferation, Dendritic Cells, Galactosylceramides, Immunization, Injections, Intraperitoneal, Lactic Acid, Mice, Mice, Inbred C57BL, Microscopy, Atomic Force, Nanoparticles, Ovalbumin, Polyglycolic Acid, Polylactic Acid-Polyglycolic Acid Copolymer, T-Lymphocytes, Vaccines
Show Abstract · Added March 21, 2018
The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova) and an adjuvant within the poly(lactic-co-glycolic acid) nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days. The in vivo immunization studies exhibited that the nanovaccine induced stronger and longer immune responses compared to its soluble counterpart. Similarly, intranasal inhalation of the nanovaccine induced more robust antigen-specific CD8 T cell response than intraperitoneal injection of nanovaccine.
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19 MeSH Terms
Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.
Tian M, Cheng C, Chen X, Duan H, Cheng HL, Dao M, Sheng Z, Kimble M, Wang L, Lin S, Schmidt SD, Du Z, Joyce MG, Chen Y, DeKosky BJ, Chen Y, Normandin E, Cantor E, Chen RE, Doria-Rose NA, Zhang Y, Shi W, Kong WP, Choe M, Henry AR, Laboune F, Georgiev IS, Huang PY, Jain S, McGuire AT, Georgeson E, Menis S, Douek DC, Schief WR, Stamatatos L, Kwong PD, Shapiro L, Haynes BF, Mascola JR, Alt FW
(2016) Cell 166: 1471-1484.e18
MeSH Terms: Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, B-Lymphocytes, Broadly Neutralizing Antibodies, Cell Line, Disease Models, Animal, Gene Expression Regulation, HIV Antibodies, HIV-1, Immunization, Immunoglobulin Heavy Chains, Inhibitory Concentration 50, Mice, Precursor Cells, B-Lymphoid, Sequence Deletion, T-Lymphocytes
Show Abstract · Added May 3, 2017
The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2 immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via targeting the CD4 binding site of the envelope glycoprotein gp120. We now describe a mouse vaccination model that allows a germline human IGHV1-2(∗)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. When sequentially immunized with modified gp120 glycoproteins designed to engage VRC01 germline and intermediate antibodies, IGHV1-2(∗)02-rearranging mice, which also express a VRC01-antibody precursor light chain, can support the affinity maturation of VRC01 precursor antibodies into HIV-neutralizing antibody lineages.
Copyright © 2016 Elsevier Inc. All rights reserved.
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17 MeSH Terms
A peptide immunization approach to counteract a Staphylococcus aureus protease defense against host immunity.
Jordan RE, Fernandez J, Brezski RJ, Greenplate AR, Knight DM, Raju TS, Lynch AS
(2016) Immunol Lett 172: 29-39
MeSH Terms: Abscess, Animals, Bacterial Load, Disease Models, Animal, Drug Combinations, Freund's Adjuvant, Hemocyanins, Humans, Immune Evasion, Immunity, Humoral, Immunization, Immunoglobulin G, Peptide Fragments, Plant Extracts, Proteolysis, Rabbits, Recombinant Fusion Proteins, Staphylococcal Infections, Staphylococcus aureus
Show Abstract · Added April 22, 2016
Pathogens that induce acute and chronic infections, as well as certain cancers, employ numerous strategies to thwart host cellular and humoral immune defenses. One proposed evasion mechanism against humoral immunity is a localized expression of extracellular proteases that cleave the IgG hinge and disable host IgG functions. Host immunity appears to be prepared to counter such a proteolytic tactic by providing a group of autoantibodies, denoted anti-hinge antibodies that specifically bind to cleaved IgGs and provide compensating functional restoration in vitro. These respective counter-measures highlight the complex interrelationships among pathogens and host immunity and suggested to us a possible means for therapeutic intervention. In this study, we combined an investigation of pathogen-mediated proteolysis of host IgGs with an immunization strategy to boost host anti-hinge antibodies. In a Staphylococcus aureus infection model using an artificial tissue cage (wiffle ball) implanted into rabbits, cleaved rabbit IgGs were detected in abundance in the abscesses of untreated animals early after infection. However, in animals previously immunized with peptide analogs of the cleaved IgG hinge to generate substantial anti-hinge antibody titers, S. aureus colony formation was markedly reduced compared to control animals or those similarly immunized with a scrambled peptide sequence. The results of this study demonstrate that extensive local proteolysis of IgGs occurs in a test abscess setting and that immunization to increase host anti-hinge antibodies provided substantial acute protection against bacterial growth.
Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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19 MeSH Terms
Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus.
Smith SA, Silva LA, Fox JM, Flyak AI, Kose N, Sapparapu G, Khomandiak S, Khomadiak S, Ashbrook AW, Kahle KM, Fong RH, Swayne S, Doranz BJ, McGee CE, Heise MT, Pal P, Brien JD, Austin SK, Diamond MS, Dermody TS, Crowe JE
(2015) Cell Host Microbe 18: 86-95
MeSH Terms: Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Chemoprevention, Chikungunya Fever, Chikungunya virus, Disease Models, Animal, Humans, Immunization, Passive, Inhibitory Concentration 50, Mice, Protein Binding, Survival Analysis, Treatment Outcome, Viral Envelope Proteins, Virus Internalization
Show Abstract · Added January 26, 2016
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.
Copyright © 2015 Elsevier Inc. All rights reserved.
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17 MeSH Terms
The case for conducting a randomized clinical trial to assess the efficacy of a single dose of prophylactic HPV vaccines among adolescents.
Kreimer AR, Sherman ME, Sahasrabuddhe VV, Safaeian M
(2015) J Natl Cancer Inst 107:
MeSH Terms: Adolescent, Cost-Benefit Analysis, Dose-Response Relationship, Drug, Female, Humans, Immunization Schedule, Papillomavirus Infections, Papillomavirus Vaccines, Randomized Controlled Trials as Topic, Research Design, United States, Uterine Cervical Neoplasms
Added March 17, 2015
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12 MeSH Terms
Alternative dosage schedules with HPV virus-like particle vaccines.
Stanley MA, Sudenga SL, Giuliano AR
(2014) Expert Rev Vaccines 13: 1027-38
MeSH Terms: Dose-Response Relationship, Immunologic, Humans, Immunization, Immunization Schedule, Papillomavirus Infections, Papillomavirus Vaccines, Vaccines, Virus-Like Particle
Show Abstract · Added August 15, 2017
HPV vaccines can prevent multiple cancers in women and men. Difficulties in the cost and completion of the three-dose vaccine series have led to considerations of alternative dose schedules. In clinical trials, three doses given within a 12-month period versus the standard 6-month period yielded comparable results, and immunogenicity appears comparable with two doses in adolescent females compared to the three-dose series in adult females. While the data are generally supportive of moving to a two-dose vaccine schedule among young female adolescents, the adoption of a two-dose vaccine schedule still poses a potential risk to the strength and longevity of the immune response. Public health authorities implementing a two-dose vaccine schedule should devise risk management strategies to minimize the potential impact on cancer prevention.
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7 MeSH Terms