scholarly journals 26. Is There a Correlation Between Reactogenicity and Immune Responses of the Adjuvanted Recombinant Zoster Vaccine (RZV)? A Post-hoc Analysis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S136-S136
Author(s):  
Andrea Callegaro ◽  
David O Willer ◽  
Wivine Burny ◽  
Caroline Hervé ◽  
Joon Hyung Kim ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Surrogate Marker ◽  
Cell Mediated Immunity ◽  
Global Score ◽  
Post Dose ◽  
Post Vaccination ◽  
Material Support ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background RZV (GSK) contains the varicella-zoster virus antigen glycoprotein E (gE) and the adjuvant system AS01B that enhances gE-specific immune responses through stimulating innate immunity. AS01B may contribute to the development of transient local or systemic post-vaccination reactions. A hypothesis that the magnitude of those reactions is predictive of immunogenicity and efficacy (i.e., “no pain, no gain”) remains untested. To evaluate potential correlations between RZV’s reactogenicity and immunogenicity in adults aged ≥ 50 years, a post-hoc analysis was conducted using data from 2 large phase 3 studies (NCT01165177, NCT01165229). Methods Reactogenicity was calculated as a single score per symptom (maximum grade recorded over 7 days post-vaccination). A global score obtained by adding each maximum severity for all reported symptoms (multivariate reactogenicity models) and a score for each reactogenicity symptom (univariate reactogenicity models) were estimated. Results The analysis included 904 and 147 RZV recipients with completed post-vaccination symptom diary cards and with anti-gE antibody results or cell-mediated immunity (CMI) results, respectively. The global score of reactogenicity post-dose 2 was significantly associated with anti-gE antibody response (p< 0.001, estimate 0.112) although the absolute antibody increase associated with reactogenicity was minimal (1.29-fold increase), while the association with CMI response was not statistically significant (p=0.073, estimate 0.230). There was a weak, but statistically significant association between gE-specific immune responses and the maximum pain post-dose 2 score (p=0.001, estimate 0.041), irrespective of post-vaccination time. Nevertheless, there are observations of immune responses in participants for whom pain was not reported. Conclusion A weak but statistically significant correlation was found between injection site pain intensity and immune responses in adult RZV recipients aged ≥ 50 years. However, participants reporting no pain were also able to mount a strong immune response, therefore pain cannot be a surrogate marker to inform on the level of immune response or on likelihood of being protected against herpes zoster. Funding GlaxoSmithKline Biologicals SA Disclosures Andrea Callegaro, PhD, GSK group of companies (Employee, Shareholder) David O. Willer, PhD, GSK group of companies (Employee, Other Financial or Material Support, Receive GSK shares as part of employment renumeration) Wivine Burny, PhD, GSK group of companies (Employee) Caroline Hervé, PhD, GSK group of companies (Employee) Joon Hyung Kim, MD, GSK group of companies (Employee, Shareholder) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support) Toufik Zahaf, PhD, GSK group of companies (Employee, Shareholder) Anthony L. Cunningham, F.A.H.M.S., MD, M.B.B.S., B. Med. Sci. (Hons), F.R.A.C.P., F.R.C.P.A., F.A.S.M., GSK group of companies (Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau) Arnaud Didierlaurent, PhD, GSK group of companies (Other Financial or Material Support, previous employee until 03/2020)Sanofi (Speaker’s Bureau)

scholarly journals Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn’s Disease: A Post Hoc Analysis From the CALM Study

2020 ◽  
Vol 26 (10) ◽  
pp. 1562-1571 ◽  
Author(s):  
Walter Reinisch ◽  
Remo Panaccione ◽  
Peter Bossuyt ◽  
Filip Baert ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Surrogate Marker ◽  
Fecal Calprotectin ◽  
Sensitivity Analyses ◽  
End Points ◽  
Predictive Values ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Disease Location

Abstract Background CALM was a randomized phase 3 trial in patients with Crohn’s disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. Results The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization. Conclusion This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD.

scholarly journals Efficacy and serious adverse events profile of the adjuvanted recombinant zoster vaccine in adults with pre-existing potential immune-mediated diseases: a pooled post hoc analysis on two parallel randomized trials

Rheumatology ◽  
2020 ◽  
Author(s):  
Alemnew F Dagnew ◽  
Debora Rausch ◽  
Caroline Hervé ◽  
Toufik Zahaf ◽  
Myron J Levin ◽  
...  
Keyword(s):  
Adverse Events ◽  
Age Groups ◽  
Zoster Vaccine ◽  
Post Dose ◽  
Serious Adverse Events ◽  
Post Hoc Analysis ◽  
Immune Mediated ◽  
Recombinant Zoster Vaccine ◽  
Post Hoc ◽  
Placebo Recipients

Abstract Objective In the ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials, the adjuvanted recombinant zoster vaccine (RZV) demonstrated ≥90% efficacy in preventing herpes zoster (HZ) in all age groups ≥50 years. Given the increased HZ risk associated with certain underlying autoimmune diseases or their treatment regimes, we conducted a post hoc analysis of RZV’s efficacy against HZ and safety profile [specifically, the occurrence of serious adverse events (SAEs)] in ZOE-50/70 participants who reported pre-existing potential immune-mediated diseases (pIMDs) at enrolment and were not on immunosuppressive therapies. Methods Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomized to receive two doses of RZV or placebo 2 months apart. In this subgroup analysis of participants with at least one pIMD at enrolment, the efficacy was calculated for two-dose recipients who did not develop confirmed HZ before 30 days post-dose 2. SAE occurrence was evaluated for all participants who received at least one dose. Results Of the 14 645 RZV and 14 660 placebo recipients from the ZOE-50/70 studies, 983 and 960, respectively, reported at least one pre-existing pIMD at enrolment and were included in these analyses. The most frequent pre-existing conditions were psoriasis, spondyloarthropathy and RA. Efficacy against HZ was 90.5% (95% CI: 73.5, 97.5%) overall with the lowest being 84.4% (95% CI: 30.8, 98.3%) in the 70–79-year-old age group. SAEs and fatal SAEs were similar between RZV and placebo recipients. Conclusion In ZOE-50/70 participants with pre-existing pIMDs, RZV was highly efficacious against HZ and SAE incidence was similar between RZV and placebo recipients. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT01165177 (ZOE-50), NCT01165229 (ZOE-70).

Polysaccharide Immunomodulators as Therapeutic Agents: Structural Aspects and Biologic Function

2000 ◽  
Vol 13 (4) ◽  
pp. 523-533 ◽  
Author(s):  
Arthur O. Tzianabos
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Current Treatment ◽  
Cell Mediated Immunity ◽  
Host Immune System ◽  
Treatment Regimens ◽  
Specific Polysaccharide ◽  
Biologic Function ◽  
Over 40 Years ◽  
Structural Aspects

SUMMARY Polysaccharide immunomodulators were first discovered over 40 years ago. Although very few have been rigorously studied, recent reports have revealed the mechanism of action and structure-function attributes of some of these molecules. Certain polysaccharide immunomodulators have been identified that have profound effects in the regulation of immune responses during the progression of infectious diseases, and studies have begun to define structural aspects of these molecules that govern their function and interaction with cells of the host immune system. These polymers can influence innate and cell-mediated immunity through interactions with T cells, monocytes, macrophages, and polymorphonuclear lymphocytes. The ability to modulate the immune response in an appropriate way can enhance the host's immune response to certain infections. In addition, this strategy can be utilized to augment current treatment regimens such as antimicrobial therapy that are becoming less efficacious with the advent of antibiotic resistance. This review focuses on recent studies that illustrate the structural and biologic activities of specific polysaccharide immunomodulators and outlines their potential for clinical use.

scholarly journals The Systemic and Cellular Metabolic Phenotype of Infection and Immune Response to Listeria monocytogenes

2021 ◽  
Vol 11 ◽  
Author(s):  
Robert M. Johnson ◽  
Adesola C. Olatunde ◽  
Lauren N. Woodie ◽  
Michael W. Greene ◽  
Elizabeth Hiltbold Schwartz
Keyword(s):  
Immune Response ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Immune Responses ◽  
Metabolic Pathways ◽  
Bacterial Load ◽  
Cellular Level ◽  
Metabolic Phenotype ◽  
Infection Model ◽  
Cell Mediated Immunity

It is widely accepted that infection and immune response incur significant metabolic demands, yet the respective demands of specific immune responses to live pathogens have not been well delineated. It is also established that upon activation, metabolic pathways undergo shifts at the cellular level. However, most studies exploring these issues at the systemic or cellular level have utilized pathogen associated molecular patterns (PAMPs) that model sepsis, or model antigens at isolated time points. Thus, the dynamics of pathogenesis and immune response to a live infection remain largely undocumented. To better quantitate the metabolic demands induced by infection, we utilized a live pathogenic infection model. Mice infected with Listeria monocytogenes were monitored longitudinally over the course of infection through clearance. We measured systemic metabolic phenotype, bacterial load, innate and adaptive immune responses, and cellular metabolic pathways. To further delineate the role of adaptive immunity in the metabolic phenotype, we utilized two doses of bacteria, one that induced both sickness behavior and protective (T cell mediated) immunity, and the other protective immunity alone. We determined that the greatest impact to systemic metabolism occurred during the early immune response, which coincided with the greatest shift in innate cellular metabolism. In contrast, during the time of maximal T cell expansion, systemic metabolism returned to resting state. Taken together, our findings demonstrate that the timing of maximal metabolic demand overlaps with the innate immune response and that when the adaptive response is maximal, the host has returned to relative metabolic homeostasis.

scholarly journals 28. Immunogenicity of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO™) in Participants by Age, Sex, and Baseline GP-ELISA Titer: A Post Hoc Analysis of Three Phase 2/3 Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Jakub Simon ◽  
Stephen Kennedy ◽  
Barbara Mahon ◽  
Sheri Dubey ◽  
Rebecca Grant-Klein ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Research Study ◽  
Scientific Research ◽  
Phase 2 ◽  
Post Hoc Analysis ◽  
Study Investigator ◽  
Elisa Titer ◽  
Three Phase ◽  
Post Hoc

Abstract Background The recent Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo highlights the sustained threat of EVD morbidity and mortality where healthcare and vaccine delivery are challenging. ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was developed by Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with multiple partners to prevent EVD and has been approved for human use in several countries. Methods We pooled data from three Phase 2/3 clinical trials conducted in Guinea (FLW), Sierra Leone (STRIVE), and Liberia (PREVAIL) during the 2013–2016 West African outbreak to assess immune responses using a validated assay in each of the three studies and performed a post hoc analysis by sex, age (18–50 yrs & >50 yrs) and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (< 200 & ≥200 EU/ml). The full analysis set (FAS) population included the primary immunogenicity populations (all vaccinated participants with serology data collected within an acceptable day range) from all three trials. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 14, 28, 180, and 365 postvaccination. Results In the overall population and in all subgroups, GP-ELISA and PRNT geometric mean titers increased from BL, with most peaking at Day 28 and persisting through Day 365. There were differences between males and females and between participants with BL GP-ELISA < 200 & ≥200 EU/ml. There did not appear to be a difference between age groups. Conclusion These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response up to 12 months in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in females and participants with preexisting immunity are consistent with those described in published literature for other vaccines. Disclosures Jakub Simon, MD, MS, Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Stephen Kennedy, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Scientific Research Study Investigator) Barbara Mahon, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Sheri Dubey, MS, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Rebecca Grant-Klein, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Ken Liu, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Jonathan Hartzel, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Beth-Ann Coller, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Carolee Welebob, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Mary Hanson, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee, Shareholder) Rebecca Grais, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Scientific Research Study Investigator)

scholarly journals Boosting of the SARS-CoV-2-specific immune response after vaccination with single-dose Sputnik Light vaccine

2021 ◽  
Author(s):  
Alexey A. Komissarov ◽  
Inna V. Dolzhikova ◽  
Grigory A. Efimov ◽  
Denis Y. Logunov ◽  
Olga Mityaeva ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
T Cell ◽  
Immune Responses ◽  
Antibody Response ◽  
Strong Correlation ◽  
Post Vaccination ◽  
Cell Responses ◽  
Novel Variants ◽  
Specific Igg

AbstractDespite the measures taken worldwide, COVID-19 pandemic still progresses. While efficient antiviral drugs are not yet widely available, vaccination is the best option to control the infection rate. Although this option is obvious in case of COVID-19–naïve individuals, it is still unclear when individuals who have recovered from a previous SARS-CoV-2 infection should be vaccinated and whether the vaccination raises immune responses against the coronavirus and its novel variants. Here we measured the dynamics of the antibody and T-cell responses, as well as virus neutralizing activity (VNA) in serum against two SARS-CoV-2 variants, B.1.1.1 and B.1.617.2, among 84 individuals with different COVID-19 status who were vaccinated with Sputnik Light vaccine. We showed that vaccination of individuals previously exposed to the virus considerably boosts the existing immune response. In these individuals, RBD-specific IgG titers and VNA in serum were already elevated on the 7th day after vaccination, while COVID-19–naïve individuals developed the antibody response and VNA mainly 21 days post–vaccination. Additionally, we found a strong correlation between RBD-specific IgG titers and VNA in serum, and according to these data vaccination may be recommended if the RBD-specific IgG titers drop to 142.7 BAU/mL or below. In summary, the results of the study demonstrate that vaccination is beneficial both for COVID-19–naïve and recovered individuals, especially since it raises serum VNA against the B.1.617.2 variant – one of four the SARS-CoV-2 variants of concern.

scholarly journals 08. Concomitant Administration of the Adjuvanted Recombinant Zoster Vaccine (RZV) with 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Is Safe and Does Not Interfere with Immunogenicity of Either Vaccine in Adults Aged ≥ 50 Years

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S127-S128
Author(s):  
Ji-Young Min ◽  
Agnes Mwakingwe-Omar ◽  
Megan Riley ◽  
Lifeter Yenwo Molo ◽  
Jyoti Soni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Responses ◽  
Response Rate ◽  
Concomitant Administration ◽  
Control Group ◽  
Vaccine Response ◽  
Open Label ◽  
Post Dose ◽  
Post Vaccination ◽  
Sequential Administration

Abstract Background This study assessed non-inferiority of humoral immunogenicity, reactogenicity, and safety of RZV when the 1st dose was co-administered with PCV13 in adults ≥ 50 years of age (YOA) compared to sequential administration. Methods In this phase 3b, open-label, multi-center study (NCT03439657), adults were randomized 1:1 to receive either the 1st RZV dose co-administered with PCV13 at day (D)1 and the 2nd RZV dose at month (M)2 (Co-Ad group), or PCV13 at D1, the 1st RZV dose at M2 and the 2nd RZV dose at M4 (Control group). Co-primary confirmatory objectives were: (i) vaccine response rate (VRR) to RZV at 1 month post-dose 2 in Co-Ad group; (ii) non-inferiority of humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group compared to Control group. Solicited adverse events (AEs) until D7 post-vaccination and unsolicited AEs until D30 post-vaccination were recorded. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected through 12 months post-RZV dose 2. Immunogenicity was performed in the per-protocol set (PPS) and safety analyses in the exposed set. Results Of 912 vaccinated adults, 863 were included in PPS (Co-Ad: 427; Control: 436). VRR for anti-glycoprotein E antibody concentrations was 99.1% in Co-Ad group. The predefined non-inferiority criteria for the humoral immune responses to RZV and PCV13 were met (Table 1). The overall frequency of solicited local AEs after RZV and PCV13 was comparable between Co-Ad and Control groups. Pain was the most common solicited local AE (Figure 1). The frequency of solicited general AEs was similar for the 1st RZV dose when co-administered with PCV13 or alone (57.4% vs 54.6%). Myalgia and fatigue were the most common solicited general AEs (Figure 2). The frequency (Co-Ad: 21.2%; Control: 23.1%) and nature of unsolicited AEs were balanced between groups. None of the reported SAEs, fatal SAEs, or pIMDs were vaccine-related. Table 1. Co-primary confirmatory objectives: vaccine response rate (VRR), and non-inferiority of the immune responses to RZV (1 month post-dose 2) and to PCV13 (1 month post-vaccination) in the Co-Ad group vs the Control group (per-protocol set) Figure 1. The incidence of solicited local adverse events (AEs) occurring within 7 days post-vaccination (overall/adult, exposed set) Figure 2. The incidence of solicited general adverse events (AEs) post-dose 1 occurring within 7 days post-vaccination (exposed set) Conclusion Co-administration of the 1st RZV dose with PCV13 showed non-inferior immune responses to sequential administration. The reactogenicity and safety of RZV in the Co-Ad group were within the range of the established safety profile of RZV. Co-administration of RZV with PCV13 may improve vaccination rates in ≥ 50 YOA population. Funding GlaxoSmithKline Biologicals SA Disclosures Ji-Young Min, PhD, GSK group of companies (Employee) Agnes Mwakingwe-Omar, MD, PhD, GSK group of companies (Employee) Megan Riley, PhD, GSK group of companies (Employee, Shareholder) Lifeter Yenwo Molo, BsC(hons) MSc(hons), GSK group of companies (Employee) Jyoti Soni, MA, GSK group of companies (Employee) Ginette Girard, MD, Diex Recherche Inc. Sherbrooke (Scientific Research Study Investigator) Jasur Danier, MD, GSK group of companies (Employee, Shareholder)

scholarly journals Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 142
Author(s):  
Sarah-Kim Friedrich ◽  
Rosa Schmitz ◽  
Michael Bergerhausen ◽  
Judith Lang ◽  
Lamin B. Cham ◽  
...  
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Immune Responses ◽  
Ebola Virus ◽  
Single Injection ◽  
Adaptive Immune Response ◽  
Surrogate Marker ◽  
Adaptive Immune Responses ◽  
Strong Immune Response ◽  
Adaptive Immune

Ebola virus epidemics can be effectively limited by the VSV-EBOV vaccine (Ervebo) due to its rapid protection abilities; however, side effects prevent the broad use of VSV-EBOV as vaccine. Mechanisms explaining the efficient immune activation after single injection with the VSV-EBOV vaccine remain mainly unknown. Here, using the clinically available VSV-EBOV vaccine (Ervebo), we show that the cell-intrinsic expression of the interferon-inhibitor Usp18 in CD169+ macrophages is one important factor modulating the anti-Ebola virus immune response. The absence of Usp18 in CD169+ macrophages led to the reduced local replication of VSV-EBOV followed by a diminished innate as well as adaptive immune response. In line, CD169-Cre+/ki x Usp18fl/fl mice showed reduced innate and adaptive immune responses against the VSV wildtype strain and died quickly after infection, suggesting that a lack of Usp18 makes mice more susceptible to the side effects of the VSV vector. In conclusion, our study shows that Usp18 expression in CD169+ macrophages is one important surrogate marker for effective vaccination against VSV-EBOV, and probably other VSV-based vaccines also.

Orchidectomy and the immune response II. Response of orchidectomized mice to antigens

1974 ◽  
Vol 185 (1081) ◽  
pp. 437-451 ◽  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Graft Versus Host Disease ◽  
Blood Cells ◽  
Bovine Serum ◽  
Cell Mediated Immunity ◽  
Skin Allograft ◽  
Graft Versus Host ◽  
Skin Allografts ◽  
Serum Albumen

The responses of orchidectomized mice to several antigens have been investigated. Orchid-ectomy was associated with an accelerated rejection of skin allograft, which was prevented by androgen administration, abrogated by anti-lymphocyte serum and potentiated by cyclophosphamide. Reactivity of orchidectomized mice to oxazolone, sheep red blood cells and graft versus host disease, which are limited by thymus-processed cells, was increased whereas production of antibodies to bovine serum albumen, skin allografts and pneumococcal poly-saccharide was unchanged. It is proposed that orchidectomy augments cell mediated immune responses, but has no direct effect on responses transacted mainly by B cells. The effect of cyclophosphamide may be due to the withdrawal of a restraining influence on cell mediated immunity normally exercised by humoral antibody.

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