Induction of Immune Responses with Clonal Dominance at High Antibody Levels

SummaryImmune tolerance has by several methods been induced in haemophiliacs with antibodies. A conversion of “high responders” into “low responders” was previously reported after repeated moderate factor IX doses over periods of 7-10 days in combination with cyclophosphamide and steroids in two patients with haemophilia B and inhibitors. This paper reports similar results in a heamophilia A patient by giving factor VIII, cyclophosphamide, and steroids during relatively short periods of time (7-8 days). The anamnestic response markedly decreased already following the first treatment and never exceeded a level of 1 u/ml (˜ 3 BU/ml) even when boosted with ordinary factor VIII doses for only 3 days. It is concluded that the markedly decreased secondary antibody response is most probably the result of factor VIII given at short intervals (twice a day) for periods of up to about one week when given in combination with cyclophosphamide and steroids. The same effect may be achieved by other methods. The treatment schedule suggested in the present paper is, however, simple and avoids long periods of high antibody levels. Furthermore, the total factor VIII dose used is lower than suggested in most other treatment schedules, which makes the treatment substantially less expensive.

Download Full-text

Nonhypoalbuminemic Inflammatory Bowel Disease in Dogs as Disease Model

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab064 ◽

2021 ◽

Author(s):

Juan Hernandez ◽

Elodie Rouillé ◽

Florian Chocteau ◽

Marie Allard ◽

Karine Haurogné ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Immune Responses ◽

Bowel Disease ◽

Interindividual Variability ◽

Expression Patterns ◽

Disease Model ◽

Protein Loss ◽

Tissue Concentrations ◽

Inflammatory Bowel ◽

Antibody Levels

Abstract Background The incidence of inflammatory bowel disease (IBD) is increasing worldwide, emphasizing the need of relevant models, as dogs spontaneously affected by IBD may be, for better knowledge of the disease’s physiopathology. Methods We studied 22 client-owned dogs suffering from IBD without protein loss and 14 control dogs. Biopsies were obtained from the duodenum, ileum, and colon. Inflammatory grade was assessed by histopathology, immunohistochemistry, and chemokine analysis. The expression of Toll-like receptors (TLR) in mucosa was immunohistochemically evaluated. Antibody levels against bacterial ligands (lipopolysaccharide [LPS] and flagellin) were measured in sera using enzyme-linked immunoassay. Results Dogs with IBD showed low to severe clinical disease. Histopathologically, the gut of dogs with IBD did not exhibit significant alterations compared with controls except in the colon. The number of CD3+ T lymphocytes was decreased in the ileum and colon of dogs with IBD compared with controls, whereas the numbers of Foxp3+, CD20+, and CD204+ cells were similar in the 2 groups. Three chemokines, but no cytokines, were detected at the protein level in the mucosa, and the disease poorly affected their tissue concentrations. Dogs with IBD exhibited higher serum reactivity against LPS and flagellin than controls but similar immunoreactivity against the receptors TLR4 and TLR5. In addition, TLR2 and TLR9 showed similar expression patterns in both groups of dogs. Conclusions Our data described dysregulated immune responses in dogs affected by IBD without protein loss. Despite fairly homogeneous dog cohorts, we were still faced with interindividual variability, and new studies with larger cohorts are needed to validate the dog as a model.

Download Full-text

Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace?

mBio ◽

10.1128/mbio.01339-14 ◽

2014 ◽

Vol 5 (3) ◽

Cited By ~ 28

Author(s):

Clara Maria Ausiello ◽

Antonio Cassone

Keyword(s):

Immune Responses ◽

Whooping Cough ◽

Experimental Models ◽

Adaptive Immune Responses ◽

Content Type ◽

Antigenic Composition ◽

Cell Responses ◽

Adaptive Immune ◽

Antibody Levels ◽

Stimulation Of

ABSTRACTThe resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses againstBordetella pertussisinfection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten.

Download Full-text

Neutralization breadth of SARS CoV-2 viral variants following primary series and booster SARS CoV-2 vaccines in patients with cancer

10.1101/2021.11.10.21265988 ◽

2021 ◽

Author(s):

Vivek Naranbhai ◽

Kerri J St. Denis ◽

Evan C Lam ◽

Onosereme Ofoman ◽

Wilfredo F Garcia-Beltran ◽

...

Keyword(s):

Immune Responses ◽

Primary Vaccination ◽

High Antibody ◽

Patients With Cancer ◽

Primary Series ◽

Vaccine Type ◽

High Antibody Titer ◽

Binding Antibody ◽

Alpha Beta ◽

Tumor Types

Patients with cancer are more likely to have impaired immune responses to SARS CoV-2 vaccines. We studied the breadth of responses against SARS CoV-2 variants followingly primary vaccination in 178 patients with a variety of tumor types, and after booster doses in a subset. Neutralization of alpha, beta, gamma and delta SARS-CoV-2 variants was impaired relative to wildtype (Wuhan), regardless of vaccine type. Regardless of viral variant, mRNA1273 was the most immunogenic, followed by BNT162b2 and then Ad26.COV2.S. Neutralization of more variants (breadth) was associated with higher magnitude of wildtype neutralization, and increase with time since vaccination; increased age associated with lower breadth. Anti-spike binding antibody concentrations were a good surrogate for breadth (PPV=90% at >1000U/ml). Booster SARS-CoV-2 vaccines conferred enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with current vaccines increases breadth of responses against variants.

Download Full-text

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

Circulation ◽

10.1161/circ.116.suppl_16.ii_844 ◽

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.

Download Full-text

Sexual Dimorphism Has Low Impact on the Response against Rotavirus Infection in Suckling Rats

Vaccines ◽

10.3390/vaccines8030345 ◽

2020 ◽

Vol 8 (3) ◽

pp. 345

Author(s):

Carla Morales-Ferré ◽

Ignasi Azagra-Boronat ◽

Malén Massot-Cladera ◽

Àngels Franch ◽

Margarida Castell ◽

...

Keyword(s):

Immune Response ◽

Sexual Dimorphism ◽

Breast Milk ◽

Immune Responses ◽

Rat Model ◽

Critical Factor ◽

Passive Transfer ◽

Male And Female ◽

Suckling Rats ◽

Antibody Levels

Rotaviruses (RVs) are the leading pathogens causing severe and acute diarrhea in children and animals. It is well known that sex contributes to shaping immune responses, thus it could also influence the incidence and severity of the RV infection. The aim of this study was to analyze the influence of sexual dimorphism on RV infection and its antibody (Ab) immune response in a suckling rat model. Neonatal suckling rats were intragastrically RV-inoculated and clinical indexes derived from fecal samples, as well as immune variables were evaluated. Higher severity of diarrhea, fecal weight and viral elimination were observed in males compared to females (p < 0.05). Regarding the adaptative immunity, the RV shaped the immune response to lower IgG1 levels and an increased Th1/Th2-associated Ab response (p < 0.05). Although females had lower IgG2a levels than males (p < 0.05), the specific anti-RV antibody levels were not sex influenced. In fact, at this age the passive transfer of anti-RV antibodies through breast milk was the critical factor for clustering animals, independently of their sex. It can be concluded that male and female diarrhea severity in RV infection is slightly influenced by sexual dimorphism and is not associated with the specific immune response against the virus.

Download Full-text

Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofv052 ◽

2015 ◽

Vol 2 (2) ◽

Cited By ~ 24

Author(s):

Adrian J. Reber ◽

Jin Hyang Kim ◽

Renata Biber ◽

H. Keipp Talbot ◽

Laura A. Coleman ◽

...

Keyword(s):

Older Adults ◽

B Cells ◽

Immune Responses ◽

Influenza Vaccine ◽

Hemagglutination Inhibition ◽

Negative Impact ◽

Memory B Cells ◽

Vaccine Response ◽

Vaccine Responses ◽

Antibody Levels

Abstract Background. Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods. We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008–2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results. Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG+ and IgA+ memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50–59. Conclusions. Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age.

Download Full-text

Disease patterns and immune responses in the offspring to sows with high or low antibody levels to Actinobacillus pleuropneumoniae serotype 2

Research in Veterinary Science ◽

10.1016/j.rvsc.2010.07.025 ◽

2011 ◽

Vol 91 (1) ◽

pp. 25-31 ◽

Cited By ~ 6

Author(s):

M. Sjölund ◽

M. Zoric ◽

M. Persson ◽

G. Karlsson ◽

P. Wallgren

Keyword(s):

Immune Responses ◽

Actinobacillus Pleuropneumoniae ◽

Disease Patterns ◽

Antibody Levels

Download Full-text

Mathematical Modeling of Immune Responses against SARS-CoV-2 Using an Ensemble Kalman Filter

Mathematics ◽

10.3390/math9192427 ◽

2021 ◽

Vol 9 (19) ◽

pp. 2427

Author(s):

Rabih Ghostine ◽

Mohamad Gharamti ◽

Sally Hassrouny ◽

Ibrahim Hoteit

Keyword(s):

Kalman Filter ◽

Viral Load ◽

Immune Responses ◽

Ensemble Kalman Filter ◽

Plasma Cells ◽

Equilibrium Points ◽

Infected Cells ◽

Many Sources ◽

Antibody Levels ◽

Assimilation System

In this paper, a mathematical model was developed to simulate SARS-CoV-2 dynamics in infected patients. The model considers both the innate and adaptive immune responses and consists of healthy cells, infected cells, viral load, cytokines, natural killer cells, cytotoxic T-lymphocytes, B-lymphocytes, plasma cells, and antibody levels. First, a mathematical analysis was performed to discuss the model’s equilibrium points and compute the basic reproduction number. The accuracy of such mathematical models may be affected by many sources of uncertainties due to the incomplete representation of the biological process and poorly known parameters. This may strongly limit their performance and prediction skills. A state-of-the-art data assimilation technique, the ensemble Kalman filter (EnKF), was then used to enhance the model’s behavior by incorporating available data to determine the best possible estimate of the model’s state and parameters. The proposed assimilation system was applied on the real viral load datasets of six COVID-19 patients. The results demonstrate the efficiency of the proposed assimilation system in improving the model predictions by up to 40%.

Download Full-text

Direct Comparison of Antibody Responses to Four SARS-CoV-2 Vaccines in Mongolia

10.1101/2021.08.22.21262161 ◽

2021 ◽

Author(s):

Naranjargal J. Dashdorj ◽

Oliver F. Wirz ◽

Katharina Roeltgen ◽

Emily Haraguchi ◽

Anthony S. Buzzanco ◽

...

Keyword(s):

Antibody Responses ◽

Health Interventions ◽

High Antibody ◽

Antibody Testing ◽

Public Health Interventions ◽

Vaccine Responses ◽

Blocking Activity ◽

Antibody Titers ◽

Alpha Variant ◽

Antibody Levels

Different vaccines for SARS-CoV-2 are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four Covid vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant RBD proteins reveal marked differences in the vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control the COVID-19 pandemic in Mongolia and worldwide.

Download Full-text