scholarly journals Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and enhance protection of anti-CSP monoclonal antibodies

2021 ◽  
Author(s):  
Brandon K. Wilder ◽  
Vladimir Vigdorovich ◽  
Sara Carbonetti ◽  
Nana Minkah ◽  
Nina Hertoghs ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Surface Protein ◽  
Major Protein ◽  
High Antibody ◽  
Related Disease ◽  
Malaria Vaccines ◽  
Promising Strategy ◽  
Disease Reduction ◽  
Antibody Titers ◽  
Sporozoite Infection

Vaccine-induced sterilizing protection from infection with the Plasmodium parasite, the pathogen that causes malaria, will be an essential tool in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection. While such disease reduction is important, these results also indicate that further improvements to vaccines based solely on CSP will likely yield diminishing benefits towards the goal of durable, infection-blocking immunity. Here, we show that monoclonal antibodies (mAbs) recognizing the sporozoite protein TRAP/SSP2 across the major protein domains exhibit a range of inhibitory capacity and that these mAbs can augment CSP-based protection despite delivering no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.

scholarly journals Immunization of Saimiri sciureus Monkeys with a Recombinant Hybrid Protein Derived from the Plasmodium falciparum Antigen Glutamate-Rich Protein and Merozoite Surface Protein 3 Can Induce Partial Protection with Freund and Montanide ISA720 Adjuvants

2005 ◽  
Vol 12 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Leonardo J. M. Carvalho ◽  
Francisco A. Alves ◽  
Cesare Bianco ◽  
Salma G. Oliveira ◽  
Graziela M. Zanini ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Challenge Infection ◽  
Saimiri Sciureus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hybrid Protein ◽  
High Antibody ◽  
Partial Protection ◽  
Antibody Titers

ABSTRACT The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end of the glutamate-rich protein (GLURP) and the C-terminal portion of the merozoite surface protein 3 (MSP3) of Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. The GLURP/MSP3 hybrid protein, expressed in Lactococcus lactis, was administered in association with alum, Montanide ISA720, or complete or incomplete Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (enzyme-linked immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge infection with P. falciparum FUP strain, all five monkeys from the GLURP/MSP3-alum group showed a rapid increase in parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-Montanide ISA720 had a delay in the course of parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group, parasitemia remained below this threshold in four of the five animals and, after it reached a peak, parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge infection boosted the antibody titers, and the importance of this event for vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against malaria infection if antibodies are induced at properly high titers.

scholarly journals Quantitative Proteomic Profiling of Small Molecule Treated Mesenchymal Stem Cells Using Chemical Probes

2020 ◽  
Vol 22 (1) ◽  
pp. 160
Author(s):  
Jerran Santos ◽  
Sibasish Dolai ◽  
Matthew B. O’Rourke ◽  
Fei Liu ◽  
Matthew P. Padula ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ribosomal Proteins ◽  
Surface Protein ◽  
Temporal Analysis ◽  
Phenotypic Characterization ◽  
Major Protein ◽  
Adipose Derived Stem Cells ◽  
Protein Markers ◽  
Proteomic Profiling ◽  
Depth Analysis

The differentiation of human adipose derived stem cells toward a neural phenotype by small molecules has been a vogue topic in the last decade. The characterization of the produced cells has been explored on a broad scale, examining morphological and specific surface protein markers; however, the lack of insight into the expression of functional proteins and their interactive partners is required to further understand the extent of the process. The phenotypic characterization by proteomic profiling allows for a substantial in-depth analysis of the molecular machinery induced and directing the cellular changes through the process. Herein we describe the temporal analysis and quantitative profiling of neural differentiating human adipose-derived stem cells after sub-proteome enrichment using a bisindolylmaleimide chemical probe. The results show that proteins enriched by the Bis-probe were identified reproducibly with 133, 118, 126 and 89 proteins identified at timepoints 0, 1, 6 and 12, respectively. Each temporal timepoint presented several shared and unique proteins relative to neural differentiation and their interactivity. The major protein classes enriched and quantified were enzymes, structural and ribosomal proteins that are integral to differentiation pathways. There were 42 uniquely identified enzymes identified in the cells, many acting as hubs in the networks with several interactions across the network modulating key biological pathways. From the cohort, it was found by gene ontology analysis that 18 enzymes had direct involvement with neurogenic differentiation.

PASSIVE IMMUNIZATION

PEDIATRICS ◽  
1963 ◽  
Vol 32 (4) ◽  
pp. 599-609
Author(s):  
Geoffrey Edsall
Keyword(s):  
Diphtheria Toxin ◽  
Gamma Globulin ◽  
Passive Immunization ◽  
Gas Gangrene ◽  
High Antibody ◽  
Antibody Titers ◽  
The Subject ◽  
Guiding Principles ◽  
Routine Procedures ◽  
The Ideal

Passive immunization has existed for over 70 years, ever since Von Behring and Kitasato demonstrated its effectiveness in neutralizing diphtheria toxin. In fact, at first glance one might think that there was little new to say on this subject. However, the very fact that its concepts and practices have been so long accepted and–in the minds of many–have fallen into the pattern of purely routine procedures, is in itself sufficient justification to re-examine the subject. In addition, moreover, there have been a number of changes in the range of diseases for which passive immunization may be employed, the type of antiserum used, and the guiding principles for use of such preparations. Therefore, it may be timely to deal with some of the present considerations that apply to passive immunization, its prospects, its scope, and its limitations. At the risk of repeating old and familiar cliches it appears desirable to summarize, at first, the guiding principles which apply to the effectiveness (or ineffectiveness) of passive immunization. First of all, it is well established that some techniques of passive immunization are highly effective–e.g., diphtheria prophylaxis with antitoxin; some are very useful but fall short of the ideal of routine success with the purpose intended–e.g., the use of gamma-globulin for the modification of measles; whereas others are of relatively uncertain value so that their usefulness in medical practice still continues to be debated–e.g., gas gangrene antitoxin. The reasons for such great disparity in the efficacy of different antisera cannot easily be put into generalizations, but surely the varied pathogenesis of the diseases in question must be a major factor, as well as the fact that high antibody titers can readily be obtained for some such sera, whereas they are difficult or impossible to achieve with others.

scholarly journals Can we predict antibody responses in SARS-CoV-2? A cohort analysis

2021 ◽  
Author(s):  
Mary Gaeddert ◽  
Philip Kitchen ◽  
Tobias Broger ◽  
Stefan Weber ◽  
Ralf Bartenschlager ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Cohort Analysis ◽  
Antibody Responses ◽  
High Antibody ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Median Increase ◽  
Antibody Titers

AbstractBackgroundAfter infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.MethodsWe recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.Results281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.ConclusionsWhile age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.

Abstract 3712: A Randomized Placebo-Controlled Trial of a Conjugate Nicotine Vaccine (NicVAX®) in Smokers Who Want to Quit: 12 Month Results

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stephen I Rennard ◽  
Douglas E Jorenby ◽  
David Gonzales ◽  
Nancy A Rigotti ◽  
Arjen de Vos ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Group Analysis ◽  
High Responder ◽  
High Antibody ◽  
Continuous Abstinence ◽  
Antibody Titers ◽  
Double Blinded ◽  
Antibody Levels

Background: Cigarette smoking triples the risk of dying from heart disease among middle-aged men and women. A nicotine vaccine (NicVAX®) has been developed to produce nicotine-specific antibodies as a means of reducing entry of nicotine into the brain as an aid to smoking cessation. Objective: To assess 12-month safety, efficacy and immunogenicity of NicVAX in smokers who want to quit. Method: Randomized, double-blinded, placebo-controlled multicenter clinical trial with 2 dose levels of NicVAX (200μg & 400μg) and 2 schedules. Generally healthy adults who smoked ≥ 15 cigarettes/day were recruited. Subjects were randomized 2:1, active:placebo, at 9 sites in the US. The primary endpoint was self reported continuous abstinence for weeks 19 – 26 confirmed by expired CO levels of ≤ 8 ppm. Secondary endpoints include point prevalence abstinence at 12 months. Results: 301 subjects (52% female) with a mean age of 48, smoking on average 24 cigarettes/day were enrolled. A pre-defined analysis of antibody levels for subjects receiving NicVAX were reviewed and divided into low and high responder groups, with the top 30 th percentile representing the high responder group. Analysis for the primary endpoint demonstrated that 15/61 (24.6%) of subjects having the highest antibody titers achieved an 8 week period of continuous abstinence between weeks 19 –26, compared to 13/100 (13.0%) for the subjects who received placebo (p=0.04). In contrast, the quit rate for those subjects that did not achieve a high antibody titer was not significantly different from placebo (14/140, 10%). There was a significant relationship between anti-nicotine antibody levels and continuous abstinence from smoking (p=0.0001). NicVAX was well-tolerated and showed no differences in adverse events or in local/systemic reactions between placebo and each active vaccine group. Conclusion: Proof-of-concept has been established by the strong correlation of high antibody titers with smoking abstinence. Interim data (6 months post vaccination) demonstrate that generating antibodies to nicotine may be a useful approach for aiding smoking cessation. This study will be completed in Sept 2007. Immunogenicity, sustained smoking cessation and relapse rates at 12 months after vaccination will be presented.

scholarly journals Rhipicephalus (Boophilus) microplus: expression and characterization of Bm86-CG in Pichia pastoris

2011 ◽  
Vol 20 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Rodrigo Casquero Cunha ◽  
Renato Andreotti ◽  
Fábio Pereira Leivas Leite
Keyword(s):  
Pichia Pastoris ◽  
Boophilus Microplus ◽  
Economic Losses ◽  
Cattle Tick ◽  
High Antibody ◽  
Western Blot Assay ◽  
Development Of Resistance ◽  
Cattle Ticks ◽  
Antibody Titers

The cattle tick Rhipicephalus (Boophilus) microplus is responsible for great economic losses. It is mainly controlled chemically, with limitations regarding development of resistance to the chemicals. Vaccines may help control this parasite, thereby reducing tick pesticide use. In this light, we performed subcloning of the gene of the protein Bm86-GC, the homologue protein that currently forms the basis of vaccines (GavacTM and TickGardPLUS) that have been developed against cattle ticks. The subcloning was done in the pPIC9 expression vector, for transformation in the yeast Pichia pastoris. This protein was characterized by expression of the recombinant Mut+ strain, which expressed greater quantities of protein. The expressed protein (rBm86-CG) was recognized in the Western-blot assay using anti-Gavac, anti-TickGard, anti-larval extract and anti-rBm86-CG polyclonal sera. The serum produced in cattle vaccinated with the antigen CG rBm86 presented high antibody titers and recognized the native protein. The rBm86-GC has potential relevance as an immunogen for vaccine formulation against cattle ticks.

scholarly journals A Histoplasma capsulatum-Specific IgG1 Isotype Monoclonal Antibody, H1C, to a 70-Kilodalton Cell Surface Protein Is Not Protective in Murine Histoplasmosis

2010 ◽  
Vol 17 (7) ◽  
pp. 1155-1158 ◽  
Author(s):  
Livia Cristina Liporagi Lopes ◽  
Allan J. Guimarães ◽  
Mariana Duarte de Cerqueira ◽  
Beatriz L. Gómez ◽  
Joshua D. Nosanchuk
Keyword(s):  
Nitric Oxide ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Histoplasma Capsulatum ◽  
Fungal Growth ◽  
Surface Protein ◽  
Cell Surface Protein ◽  
Fungal Burden ◽  
Nitric Oxide Release ◽  
Igg1 Isotype

ABSTRACT Monoclonal antibodies to Histoplasma capsulatum can modify pathogenesis. We now show that monoclonal antibody H1C to a 70-kDa antigen increases intracellular fungal growth and reduces macrophage nitric oxide release but has no effect on fungal burden or survival in murine infection. This further demonstrates the complexities of host-pathogen interactions.

scholarly journals Antigenic Change in Human Influenza A(H2N2) Viruses Detected by Using Human Plasma from Aged and Younger Adult Individuals

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 978 ◽  
Author(s):  
Matsuzawa ◽  
Iwatsuki-Horimoto ◽  
Nishimoto ◽  
Abe ◽  
Fukuyama ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Plasma ◽  
Influenza A ◽  
Neutralizing Antibody ◽  
Plasma Samples ◽  
Human Influenza ◽  
Human Monoclonal Antibodies ◽  
Younger Adults ◽  
Antibody Titers ◽  
Antigenic Cartography

Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.

scholarly journals Human Monoclonal Antibodies againstPseudomonas aeruginosa Lipopolysaccharide Derived from Transgenic Mice Containing Megabase Human Immunoglobulin Loci Are Opsonic and Protective against Fatal Pseudomonas Sepsis

2001 ◽  
Vol 69 (4) ◽  
pp. 2223-2229 ◽  
Author(s):  
Sonali Hemachandra ◽  
Kulwant Kamboj ◽  
Janna Copfer ◽  
Gerald Pier ◽  
Larry L. Green ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Variable Region ◽  
Human Immunoglobulin ◽  
High Avidity ◽  
Genes Encoding ◽  
Antibody Titers ◽  
Multiple Donors ◽  
Human Polymorphonuclear Leukocytes ◽  
Variable Region Genes

ABSTRACT Pseudomonas aeruginosa is a significant human pathogen, and no vaccine is commercially available. Passive antibody prophylaxis using monoclonal antibodies (MAb) against protectiveP. aeruginosa epitopes is an alternative strategy for preventing P. aeruginosa infection, but mouse MAb are not suitable for use in humans. Polyclonal human antibodies from multiple donors have variable antibody titers, and human MAb are difficult to make. We used immunoglobulin-inactivated transgenic mice reconstituted with megabase-size human immunoglobulin loci to generate a human MAb against the polysaccharide (PS) portion of the lipopolysaccharide O side chain of a common pathogenic serogroup ofP. aeruginosa, 06ad. The anti-PS human immunoglobulin G2 MAb made from mice immunized with heat-killed P. aeruginosa was specific for serogroup 06ad pseudomonas. The MAb was highly opsonic for the uptake and killing of P. aeruginosa by human polymorphonuclear leukocytes in the presence of human complement. In addition, 25 μg of the MAb protected 100% of neutropenic mice from fatal P. aeruginosasepsis. DNA sequence analysis of the genes encoding the MAb revealed VH3 and Vκ2/A2 variable-region genes, similar to variable-region genes in humans immunized with bacterial PS and associated with high-avidity anti-PS antibodies. We conclude that human MAb to P. aeruginosa made in these transgenic mice are highly protective and that these mice mimic the antibody response seen in humans immunized with T-cell-independent antigens such as bacterial PS.

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