scholarly journals Revealing how variations in antibody repertoires correlate with vaccine responses

2021 ◽  
Author(s):  
Yana Safonova ◽  
Sung Bong Shin ◽  
Luke Kramer ◽  
James Reecy ◽  
Corey T. Watson ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Large Fraction ◽  
Immunoglobulin Genes ◽  
Vaccine Response ◽  
Breeding Programs ◽  
Vaccine Responses ◽  
Important Challenge ◽  
Antibody Repertoires ◽  
Selection Of

An important challenge in vaccine development is to figure out why a vaccine succeeds in some individuals and fails in others. Although antibody repertoires hold a key to answering this question, there have been very few personalized immunogenomics studies so far aimed at revealing how variations in immunoglobulin genes affect a vaccine response. We conducted an immunosequencing study of 204 calves vaccinated against bovine respiratory disease (BRD) with the goal to reveal variations in immunoglobulin genes and somatic hypermutations that impact the efficacy of vaccine response. Our study represents the largest longitudinal personalized immunogenomics study reported to date across all species, including humans. To analyze the generated dataset, we developed an algorithm for identifying variations of the immunoglobulin genes (as well as frequent somatic hypermutations) that affect various features of the antibody repertoire and titers of neutralizing antibodies. In contrast to relatively short human antibodies, cattle have a large fraction of ultralong antibodies that have opened new therapeutic opportunities. Our study revealed that ultralong antibodies are a key component of the immune response against the costliest disease of beef cattle in North America. The detected variants of the cattle immunoglobulin genes, which are implicated in the success/failure of the BRD vaccine, have the potential to direct the selection of individual cattle for ongoing breeding programs.

scholarly journals Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

2020 ◽  
Vol 11 ◽  
Author(s):  
Casey P. Shannon ◽  
Travis M. Blimkie ◽  
Rym Ben-Othman ◽  
Nicole Gladish ◽  
Nelly Amenyogbe ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Vaccine Development ◽  
Effective Means ◽  
Interaction Network ◽  
Effective Vaccine ◽  
Molecular Characteristics ◽  
Vaccine Response ◽  
Hbv Vaccine ◽  
Fecal Microbiome ◽  
Vaccine Responses

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

scholarly journals Persistence of Neutralizing Antibodies to SARS-CoV-2 in First Wave Infected Individuals at Ten Months Post-Infection: The UnIRSA Cohort Study

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2270
Author(s):  
Gloria Griffante ◽  
Shikha Chandel ◽  
Daniela Ferrante ◽  
Valeria Caneparo ◽  
Daniela Capello ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Natural Infection ◽  
Large Fraction ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Northern Italy ◽  
Serum Samples ◽  
Neutralization Titer ◽  
Igg Antibody

Longitudinal mapping of antibody-based SARS-CoV-2 immunity is critical for public health control of the pandemic and vaccine development. We performed a longitudinal analysis of the antibody-based immune response in a cohort of 100 COVID-19 individuals who were infected during the first wave of infection in northern Italy. The SARS-CoV-2 humoral response was tested using the COVID-SeroIndex, Kantaro Quantitative SARS-CoV-2 IgG Antibody RUO Kit (R&D Systems, Bio-Techne, Minneapolis, USA) and pseudotype-based neutralizing antibody assay. Using sequential serum samples collected from 100 COVID-19 recovered individuals from northern Italy—mostly with mild disease—at 2 and 10 months after their first positive PCR test, we show that 93% of them seroconverted at 2 months, with a geometric mean (GeoMean) half-maximal neutralization titer (NT50) of 387.9. Among the 35 unvaccinated subjects retested at 10 months, 7 resulted seronegative, with an 80% drop in seropositivity, while 28 showed decreased anti-receptor binding domain (RBD) and anti-spike (S) IgG titers, with a GeoMean NT50 neutralization titer dropping to 163.5. As an NT50 > 100 is known to confer protection from SARS-CoV-2 re-infection, our data show that the neutralizing activity elicited by the natural infection has lasted for at least 10 months in a large fraction of subjects.

scholarly journals Immunizations with Enterotoxigenic Escherichia coli Heat-Stable Toxin Conjugates Engender Toxin-Neutralizing Antibodies in Mice That Also Cross-React with Guanylin and Uroguanylin

2019 ◽  
Vol 87 (7) ◽  
Author(s):  
Yuleima Diaz ◽  
Morten L. Govasli ◽  
Ephrem Debebe Zegeye ◽  
Halvor Sommerfelt ◽  
Hans Steinsland ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Cross Reactivity ◽  
Enterotoxigenic Escherichia Coli ◽  
Middle Income ◽  
Content Type ◽  
Endogenous Peptides ◽  
Heat Stable ◽  
Important Challenge

ABSTRACT Infection with enterotoxigenic Escherichia coli (ETEC) is a common cause of childhood diarrhea in low- and middle-income countries, as well as of diarrhea among travelers to these countries. In children, ETEC strains secreting the heat-stable toxin (ST) are the most pathogenic, and there are ongoing efforts to develop vaccines that target ST. One important challenge for ST vaccine development is to construct immunogens that do not elicit antibodies that cross-react with guanylin and uroguanylin, which are endogenous peptides involved in regulating the activity of the guanylate cyclase-C (GC-C) receptor. We immunized mice with both human ST (STh) and porcine ST (STp) chemically coupled to bovine serum albumin, and the resulting sera neutralized the toxic activities of both STh and STp. This suggests that a vaccine based on either ST variant can confer cross-protection. However, several anti-STh and anti-STp sera cross-reacted with the endogenous peptides, suggesting that the ST sequence must be altered to reduce the risk of unwanted cross-reactivity. Epitope mapping of four monoclonal anti-STh and six anti-STp antibodies, all of which neutralized both STh and STp, revealed that most epitopes appear to have at least one amino acid residue shared with guanylin or uroguanylin. Despite this, only one monoclonal antibody displayed demonstrable cross-reactivity to the endogenous peptides, suggesting that targeted mutations of a limited number of ST residues may be sufficient to obtain a safe ST-based vaccine.

scholarly journals Vaccines against Coronavirus Disease: Target Proteins, Immune Responses, and Status of Ongoing Clinical Trials

2020 ◽  
Vol 14 (4) ◽  
pp. 2253-2263
Author(s):  
Rike Syahniar ◽  
Maria Berlina Purba ◽  
Heri Setiyo Bekti ◽  
Mardhia Mardhia
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Host Cells ◽  
Rapid Transmission ◽  
Adequate Dosage ◽  
Immunogenic Response ◽  
Selection Of

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 26 million individuals and caused 871,166 deaths globally. Various countries are racing against time to find a vaccine for controlling the rapid transmission of infection. The selection of antigen targets to trigger an immune response is crucial for vaccine development strategies. The receptor binding domain of the subunit of spike 1 protein is considered a promising vaccine candidate because of its ability to prevent attachment and infection of host cells by stimulating neutralizing antibodies. The vaccine is expected to mount a sufficient immunogenic response to eliminate the virus and store antigenic information in memory cells for long-term protection. Here, we review the ongoing clinical trials for COVID-19 vaccines and discuss the immune responses in patients administered an adequate dosage to prevent COVID-19.

scholarly journals Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population

2020 ◽  
Vol 42 (5) ◽  
pp. 619-634 ◽  
Author(s):  
Annalisa Ciabattini ◽  
Paolo Garagnani ◽  
Francesco Santoro ◽  
Rino Rappuoli ◽  
Claudio Franceschi ◽  
...  
Keyword(s):  
Older People ◽  
Elderly Population ◽  
Vaccine Development ◽  
The Elderly ◽  
Cytokine Storm ◽  
Pharmacological Treatments ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Correlates Of Protection ◽  
Age Related

AbstractThe SARS-CoV-2 pandemic urgently calls for the development of effective preventive tools. COVID-19 hits greatly the elder and more fragile fraction of the population boosting the evergreen issue of the vaccination of older people. The development of a vaccine against SARS-CoV-2 tailored for the elderly population faces the challenge of the poor immune responsiveness of the older population due to immunosenescence, comorbidities, and pharmacological treatments. Moreover, it is likely that the inflammaging phenotype associated with age could both influence vaccination efficacy and exacerbate the risk of COVID-19-related “cytokine storm syndrome” with an overlap between the factors which impact vaccination effectiveness and those that boost virulence and worsen the prognosis of SARS-CoV-2 infection. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. In the ongoing effort in vaccine development, different SARS-CoV-2 vaccine candidates have been developed, tested in pre-clinical and clinical studies and are undergoing clinical testing, but only a small fraction of these are currently being tested in the older fraction of the population. Recent advances in systems biology integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly.

scholarly journals Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings

2021 ◽  
Vol 12 ◽  
Author(s):  
Emmanuella Driciru ◽  
Jan Pieter R. Koopman ◽  
Stephen Cose ◽  
Afzal A. Siddiqui ◽  
Maria Yazdanbakhsh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Vaccine Development ◽  
Clinical Trial Design ◽  
Prior Exposure ◽  
Host Immune System ◽  
Vaccine Response ◽  
Vaccine Candidates ◽  
Vaccine Responses

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.

ESTIMASI NILAI HERITABILITAS BOBOT IKAN MAS VARIETAS PUNTEN DALAM PROGRAM SELEKSI INDIVIDU

2016 ◽  
Vol 11 (3) ◽  
pp. 217
Author(s):  
Estu Nugroho ◽  
Budi Setyono ◽  
Mochammad Su’eb ◽  
Tri Heru Prihadi
Keyword(s):  
Body Weight ◽  
Selection Response ◽  
Base Population ◽  
Breeding Programs ◽  
Male And Female ◽  
Body Weight Trait ◽  
Population Selection ◽  
Selection For ◽  
Weight Trait ◽  
Selection Of

Program pemuliaan ikan mas varietas Punten dilakukan dengan seleksi individu terhadap karakter bobot ikan. Pembentukan populasi dasar untuk kegiatan seleksi dilakukan dengan memijahkan secara massal induk ikan mas yang terdiri atas 20 induk betina dan 21 induk jantan yang dikoleksi dari daerah Punten, Kepanjen (delapan betina dan enam jantan), Kediri (tujuh betina dan 12 jantan), Sragen (27 betina dan 10 jantan), dan Blitar (15 betina dan 11 jantan). Larva umur 10 hari dipelihara selama empat bulan. Selanjutnya dilakukan penjarangan sebesar 50% dan benih dipelihara selama 14 bulan untuk dilakukan seleksi dengan panduan hasil sampling 250 ekor individu setiap populasi. Seleksi terhadap calon induk dilakukan saat umur 18 bulan pada populasi jantan dan betina secara terpisah dengan memilih berdasarkan 10% bobot ikan yang terbaik. Calon induk yang terseleksi kemudian dipelihara hingga matang gonad, kemudian dipilih sebanyak 150 pasang dan dipijahkan secara massal. Didapatkan respons positif dari hasil seleksi berdasarkan bobot ikan, yaitu 49,89 g atau 3,66% (populasi ikan jantan) dan 168,47 g atau 11,43% (populasi ikan betina). Nilai heritabilitas untuk bobot ikan adalah 0,238 (jantan) dan 0,505 (betina).Punten carp breeding programs were carried out by individual selection for body weight trait. The base population for selection activities were conducted by mass breeding of parent consisted of 20 female and 21 male collected from area Punten, eight female and six male (Kepanjen), seven female and 12 male (Kediri), 27 female and 10 male (Sragen), 15 female and 11 male (Blitar). Larvae 10 days old reared for four moths. Then after spacing out 50% of total harvest, the offspring reared for 14 months for selection activity based on the sampling of 250 individual each population. Selection of broodstock candidates performed since 18 months age on male and female populations separately by selecting based on 10% of fish with best body weight. Candidates selected broodstocks were then maintained until mature. In oder to produce the next generation 150 pairs were sets and held for mass spawning. The results revealed that selection response were positive, 49.89 g (3.66%) for male and 168.47 (11.43%) for female. Heritability for body weight is 0.238 (male) and 0.505 (female).

SARS-CoV-2 Biology Insights, Part IV.Antibody-Dependent Enhancement (ADE) and the tricky “Herd Immunity”: narrative review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Whooping Cough ◽  
Common Knowledge ◽  
Herd Immunity ◽  
Life Quality ◽  
Host Cells ◽  
System P

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.

scholarly journals Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Low Income ◽  
Controlled Trial ◽  
Interferon Γ ◽  
Population Differences ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Helminth Infections ◽  
Registration Number ◽  
Randomised Controlled

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.

scholarly journals Combining metabolomic and transcriptomic approaches to assess and improve crop quality traits

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Delphine M. Pott ◽  
Sara Durán-Soria ◽  
Sonia Osorio ◽  
José G. Vallarino
Keyword(s):  
Quality Trait ◽  
Quality Traits ◽  
Crop Species ◽  
Breeding Programs ◽  
Crop Quality ◽  
Crop Varieties ◽  
New Genes ◽  
Technical Advances ◽  
Health Promoting ◽  
Selection Of

AbstractPlant quality trait improvement has become a global necessity due to the world overpopulation. In particular, producing crop species with enhanced nutrients and health-promoting compounds is one of the main aims of current breeding programs. However, breeders traditionally focused on characteristics such as yield or pest resistance, while breeding for crop quality, which largely depends on the presence and accumulation of highly valuable metabolites in the plant edible parts, was left out due to the complexity of plant metabolome and the impossibility to properly phenotype it. Recent technical advances in high throughput metabolomic, transcriptomic and genomic platforms have provided efficient approaches to identify new genes and pathways responsible for the extremely diverse plant metabolome. In addition, they allow to establish correlation between genotype and metabolite composition, and to clarify the genetic architecture of complex biochemical pathways, such as the accumulation of secondary metabolites in plants, many of them being highly valuable for the human diet. In this review, we focus on how the combination of metabolomic, transcriptomic and genomic approaches is a useful tool for the selection of crop varieties with improved nutritional value and quality traits.

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