scholarly journals SARS-CoV-2 Infection Challenge Experiments in Nonhuman Primates: An Ethical Perspective

2021 ◽  
Author(s):  
David DeGrazia ◽  
Franklin G Miller
Keyword(s):  
Ethical Issues ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Animal Research ◽  
Therapeutic Interventions ◽  
Effective Vaccine ◽  
Ethical Perspective ◽  
Animal Research Ethics ◽  
Human Use ◽  
Scientific Endeavor

Abstract The COVID-19 pandemic has stimulated massive investment in biomedical research with the aims of understanding the disease and developing effective vaccine and therapeutic interventions. What role should animal research play in this scientific endeavor? Both the urgency to evaluate candidate interventions for human use and growing societal concern about ethical treatment of (nonhuman) animals put into question the justifiability of animal research as a precursor to clinical trials. Yet forgoing animal research in the rush to undertake human testing might expose human research participants to unacceptable risks. In this article, we apply a recently developed framework of principles for animal research ethics in exploring ethical questions raised by a SARS-CoV-2 infection challenge experiment involving rhesus macaques, which evaluated the protective efficacy of the mRNA-1273 vaccine that was recently approved for emergency use. Our aim is to illuminate the ethical issues while introducing, and illustrating the use of, the framework.

scholarly journals Protection against SHIV-KB9 Infection by Combining rDNA and rFPV Vaccines Based on HIV Multiepitope and p24 Protein in Chinese Rhesus Macaques

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Chang Li ◽  
Zhenwei Shen ◽  
Xiao Li ◽  
Jieying Bai ◽  
Lin Zeng ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Protective Efficacy ◽  
Specific Binding ◽  
Rhesus Macaques ◽  
The Body ◽  
Effective Vaccine ◽  
Preclinical Research ◽  
Aids Vaccine ◽  
Chinese Rhesus Macaques

Developing an effective vaccine against HIV infection remains an urgent goal. We used a DNA prime/fowlpox virus boost regimen to immunize Chinese rhesus macaques. The animals were challenged intramuscularly with pathogenic molecularly cloned SHIV-KB9. Immunogenicity and protective efficacy of vaccines were investigated by measuring IFN-γlevels, monitoring HIV-specific binding antibodies, examining viral load, and analyzing CD4/CD8 ratio. Results show that, upon challenge, the vaccine group can induce a strong immune response in the body, represented by increased expression of IFN-γ, slow and steady elevated antibody production, reduced peak value of acute viral load, and increase in the average CD4/CD8 ratio. The current research suggests that rapid reaction speed, appropriate response strength, and long-lasting immune response time may be key protection factors for AIDS vaccine. The present study contributes significantly to AIDS vaccine and preclinical research.

scholarly journals Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS-CoV-2 vaccine in rhesus macaques

2020 ◽  
Author(s):  
Pragya Yadav ◽  
Raches Ella ◽  
Sanjay Kumar ◽  
Dilip Patil ◽  
Sreelekshmy Mohandas ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Alveolar Epithelium ◽  
Neutralizing Antibody ◽  
Lavage Fluid ◽  
Effective Vaccine ◽  
Phase I Clinical Trials ◽  
Health Crisis ◽  
Vaccine Candidates

Abstract The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). Twenty macaques were divided into four groups of five animals each. One group was administered a placebo while three groups were immunized with three different vaccine candidates at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab, and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).

scholarly journals Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nichole R. Klatt ◽  
Courtney Broedlow ◽  
Jessica M. Osborn ◽  
Andrew T. Gustin ◽  
Sandra Dross ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Transmission ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Mucosal Vaccine ◽  
Effective Vaccine ◽  
Protein Vaccine ◽  
Viral Kinetics ◽  
Effective Strategies ◽  
Probiotic Treatment

AbstractAn effective vaccine to prevent HIV transmission has not yet been achieved. Modulation of the microbiome via probiotic therapy has been suggested to result in enhanced mucosal immunity. Here, we evaluated whether probiotic therapy could improve the immunogenicity and protective efficacy of SIV/HIV vaccination. Rhesus macaques were co-immunized with an SIV/HIV DNA vaccine via particle-mediated epidermal delivery and an HIV protein vaccine administered intramuscularly with Adjuplex™ adjuvant, while receiving daily oral Visbiome® probiotics. Probiotic therapy alone led to reduced frequencies of colonic CCR5+ and CCR6+ CD4+ T cells. Probiotics with SIV/HIV vaccination led to similar reductions in colonic CCR5+ CD4+ T cell frequencies. SIV/HIV-specific T cell and antibody responses were readily detected in the periphery of vaccinated animals but were not enhanced with probiotic treatment. Combination probiotics and vaccination did not impact rectal SIV/HIV target populations or reduce the rate of heterologous SHIV acquisition during the intrarectal challenge. Finally, post-infection viral kinetics were similar between all groups. Thus, although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses.

scholarly journals The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashwani Kesarwani ◽  
Parul Sahu ◽  
Kshama Jain ◽  
Prakriti Sinha ◽  
K. Varsha Mohan ◽  
...  
Keyword(s):  
T Cells ◽  
Macaca Mulatta ◽  
Ex Vivo ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Allergic Response ◽  
Control Group ◽  
Activated T Cells ◽  
Primate Model ◽  
Safety And Efficacy

AbstractDue to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.

scholarly journals Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
Karen V. Kibler ◽  
Benedikt Asbach ◽  
Beatriz Perdiguero ◽  
Juan García-Arriaza ◽  
Nicole L. Yates ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vaccine Candidate ◽  
Rhesus Macaques ◽  
Phase Iii ◽  
Effective Vaccine ◽  
Phase Iii Clinical Trial ◽  
Boost Regimen ◽  
Clade C ◽  
The One ◽  
Hiv 1

ABSTRACT As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial. IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.

Animal Research Ethics

2002 ◽  
Author(s):  
Kathleen Pritchett ◽  
Anna Olsson ◽  
Peter Sandøe ◽  
Paul Robinson
Keyword(s):  
Research Ethics ◽  
Animal Research ◽  
Animal Research Ethics

scholarly journals Human rights and children’s rights in worldview education in Finland

2022 ◽  
Vol 5 (1) ◽  
pp. 47-69
Author(s):  
Eero Salmenkivi ◽  
Tuija Kasa ◽  
Niina Putkonen ◽  
Arto Kallioniemi
Keyword(s):  
Human Rights ◽  
Religious Education ◽  
Core Curriculum ◽  
Ethical Issues ◽  
Children's Rights ◽  
Children’S Rights ◽  
Ethical Perspective ◽  
Specific Focus ◽  
Explicit Mention ◽  
Freedom Of Thought

In this article we examine the profiling of human rights and children’s rights in religious education (RE) and its secular alternative in Finland. We use the term ‘worldview education’ to describe the combination of these subjects. We analyse what kinds of human rights and ethical issues are raised in Finnish worldview education. One specific focus is the explicit mention of human rights and children’s rights in the worldview education section of the Finnish national core curriculum (2014). We conclude that the curriculum gives plenty of space to human rights and children’s rights, and that this enables one to conceive of human rights as being an overarching ethical perspective in worldview education. Nevertheless, we indicate that the organisation of worldview education in Finland has some problems when it comes to the realisation of children’s freedom of thought, conscience, and religion.

scholarly journals Analysis and Prospects of Using Recombinant Vaccinia Virus MVA Strain as a Vector in the Development of the Vaccines against Human and Simian Immunodeficiency Virus Diseases

2019 ◽  
pp. 37-44
Author(s):  
L. F. Stovba ◽  
V. T. Krotkov ◽  
D. I. Paveli’ev ◽  
S. A. Mel’nikov ◽  
V. N. Lebedev ◽  
...  
Keyword(s):  
Immune Response ◽  
Simian Immunodeficiency Virus ◽  
Structural Changes ◽  
Rhesus Macaques ◽  
Laboratory Animals ◽  
Cell Immune Response ◽  
Effective Vaccine ◽  
Protective Efficiency ◽  
Immunodeficiency Virus ◽  
Immunodominant Antigens

The review presents the results of preclinical use of vector vaccines against human immunodeficiency virus (HIV) disease and simian immunodeficiency virus (SIV) disease. Application of antiretroviral therapy exclusively is insufficient for elimination of HIV from patient’s body. This dictates the need for an effective vaccine which will reduce the number of new cases of the disease and reduce the risk of virus transmission. Current practice of medicinal product development showed the effectiveness of heterologous prime-boost regimens for the induction of expressed immune response in laboratory animals. Various vector constructs were used as priming vaccines: DNA vaccines, Bacille Calmette-Guerin vaccine, chimpanzee adenovirus, vesicular stomatitis virus, alphavirus repli-clone. Booster vaccine was represented by recombinant MVA strain. In all vector vaccines, different genes of immunodominant antigens of HIV and SIV agents were inserted. On rhesus macaques, murine, rabbit models, it was demonstrated that deployed vaccination schemes were safe and induced immune response. Because membrane HIV protein is highly variable, strongly glycoziled and subjected to structural changes during receptor binding, it cannot be viewed as a target for induction of virus neutralized antibodies. Therefore, we mainly studied the cell immune response that was presented by poly-functional CD8+ T-cells. However, some recent researches are aimed at such modification of envelope HIV immunogene that would provide for virus neutralizing antibody induction. The study of protective efficiency of the induced immunity in rhesus macaques, immunized with recombinant vectors expressing SIV’ s immunodominant antigens, in case of subsequent inoculation with virulent SIV strain has revealed that all monkeys developed illness. Assuming that the constructions with SIV’ s immunodominant antigens under protective efficiency testing on rhesus macaques imitate AIDS in humans, it seems that vaccines, developed up-to-date, will not be effective for collective immunity formation against AIDS. Therefore, the search for novel combinations of expressed immunodominant antigens for the inclusion into the composition of priming and booster vaccines remains a priority area at present time.

scholarly journals Development of Novel Protective Polyvalent Irradiated Pseudomonas aeruginosa Vaccine for Immuno-Compromised Patients

2021 ◽  
Vol 16 ◽  
pp. 1-10
Author(s):  
Manal M.E. Ahmed ◽  
Jakeen Eljakee ◽  
Tarek Mahran
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protective Efficacy ◽  
Challenge Test ◽  
Opportunistic Pathogen ◽  
Effective Vaccine ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Promising Strategy ◽  
Antigenic Expression ◽  
Compromised Patients

Pseudomonas aeruginosa is an opportunistic pathogen affecting immuno-compromised patients; however, no effective vaccine is currently available in the market. Here, we developed novel polyvalent irradiated P. aeruginosa vaccine using cobalt 60 that inhibited pathogen viability but retained antigenic expression functionally. Mice were vaccinated by the developed vaccine by intranasal, intramuscular and subcutaneous route of administration followed by challenge test. The protective efficacy of the novel vaccine reached up to 95%. This significant protection was mainly associated with measurable antiserum opsonic killing activity. In conclusion, the novel vaccine provides a promising strategy of both prophylactic and therapeutic approaches for immuno-compromised patients against MDR P. aeruginosa.

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