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 The Recombinant Maize Ribosome-Inactivating Protein Transiently Reduces Viral Load in SHIV89.6 Infected Chinese Rhesus Macaques

Toxins ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 156-169 ◽  
Author(s):  
Rui-Rui Wang ◽  
Ka-Yee Au ◽  
Hong-Yi Zheng ◽  
Liang-Min Gao ◽  
Xuan Zhang ◽  
...  
Keyword(s):  
Viral Load ◽  
Rhesus Macaques ◽  
Ribosome Inactivating Protein ◽  
Chinese Rhesus Macaques

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 Assembly, Biochemical Characterization, Immunogenicity, Adjuvanticity, and Efficacy ofShigellaArtificial Invaplex

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e00583-17 ◽  
Author(s):  
K. Ross Turbyfill ◽  
Kristen A. Clarkson ◽  
Anthony R. Vortherms ◽  
Edwin V. Oaks ◽  
Robert W. Kaminski
Keyword(s):  
Immune Response ◽  
Guinea Pigs ◽  
Biochemical Characterization ◽  
Diarrheal Disease ◽  
Protective Efficacy ◽  
Water Extract ◽  
Effective Vaccine ◽  
Oral Fluids ◽  
Specific Antigens ◽  
New Generation

ABSTRACTThe native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange-purified product derived from the water extract of virulentShigellaspecies. The key component of InvaplexNATis a high-molecular-mass complex (HMMC) consisting of theShigellalipopolysaccharide (LPS) and the invasin proteins IpaB and IpaC. To improve product purity and immunogenicity, artificial Invaplex (InvaplexAR) was developed using recombinant IpaB and IpaC proteins and purifiedShigellaLPS to assemble an HMMC consisting of all three components. Characterization of InvaplexARby various methods demonstrated similar characteristics as the previously reported HMMC in InvaplexNAT. The well-defined InvaplexARvaccine consistently contained greater quantities of IpaB, IpaC, and LPS than InvaplexNAT. InvaplexARand InvaplexNATimmunogenicities were compared in mouse and guinea pig dose escalation studies. In both models, immunization induced antibody responses specific for InvaplexNATand LPS while InvaplexARinduced markedly higher anti-IpaB and -IpaC serum IgG and IgA endpoint titers. In the murine model, homologous protection was achieved with 10-fold less InvaplexARthan InvaplexNATand mice receiving InvaplexARlost significantly less weight than mice receiving the same amount of InvaplexNAT. Moreover, mice immunized with InvaplexARwere protected from challenge with both homologous and heterologousShigellaserotypes. Guinea pigs receiving approximately 5-fold less InvaplexARcompared to cohorts immunized with InvaplexNATwere protected from ocular challenge. Furthermore, adjuvanticity previously attributed to InvaplexNATwas retained with InvaplexAR. The second-generationShigellaInvaplex vaccine, InvaplexAR, offers significant advantages over InvaplexNATin reproducibility, flexible yet defined composition, immunogenicity, and protective efficacy.IMPORTANCEShigellaspecies are bacteria that cause severe diarrheal disease worldwide, primarily in young children. Treatment of shigellosis includes oral fluids and antibiotics, but the high burden of disease, increasing prevalence of antibiotic resistance, and long-term health consequences clearly warrant the development of an effective vaccine. OneShigellavaccine under development is termed the invasin complex or Invaplex and is designed to drive an immune response to specific antigens of the bacteria in an effort to protect an individual from infection. The work presented here describes the production and evaluation of a new generation of Invaplex. The improved vaccine stimulates the production of antibodies in immunized mice and guinea pigs and protects these animals fromShigellainfection. The next step in the product’s development will be to test the safety and immune response induced in humans immunized with Invaplex.

scholarly journals Immunogenicity and protective efficacy of BBV152: a whole virion inactivated SARS CoV-2 vaccine in the Syrian hamster model

2020 ◽  
Author(s):  
Sreelekshmy Mohandas ◽  
Pragya D Yadav ◽  
Anita Shete ◽  
Priya Abraham ◽  
Krishna Mohan ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Effective Vaccine ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Humoral Immune ◽  
Robust Immune Response

Abstract The availability of a safe and effective vaccine would be the eventual measure to deal with SARS-CoV-2 threat. Here, we have developed and assessed the immunogenicity and protective efficacy of an inactivated SARS-CoV-2 vaccine (BBV152) in hamsters. Three dose vaccination regime with three formulations of BBV152 induced significant titres of SARS-CoV-2 specific IgG and neutralizing antibodies. The formulation with imidazoquinoline adsorbed on alum adjuvant remarkably generated a quick and robust immune response. Th1 biased immune response was demonstrated by the detection of IgG2 antibodies. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamsters was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology and robust humoral immune response. These findings confirm the immunogenic potential of BBV152 and further protection of hamsters challenged with SARS-CoV-2.

scholarly journals Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1034
Author(s):  
Ahmed O. Shalash ◽  
Luke Becker ◽  
Jieru Yang ◽  
Paul Giacomin ◽  
Mark Pearson ◽  
...  
Keyword(s):  
Immune Response ◽  
Worm Burden ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Digestive Enzyme ◽  
Peptide Vaccine ◽  
Effective Vaccine ◽  
Antigen Delivery ◽  
Hookworm Infection ◽  
Linear Arrangement

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL10 or LL10, respectively) groups as self-adjuvanting moieties. BL10 and LL10 induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL10. APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection.

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 Evaluation of Safety and Protective Efficacy of a waaJ and spiC Double Deletion Korean Epidemic Strain of Salmonella enterica Serovar Gallinarum

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun-Feng Zhang ◽  
Ke Shang ◽  
Bai Wei ◽  
Yea-Jin Lee ◽  
Jong-Yeol Park ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Virulence Gene ◽  
Oral Immunization ◽  
The Body ◽  
Deletion Strain ◽  
Effective Vaccine ◽  
Epidemic Strain ◽  
Double Deletion

With an aim to develop a highly attenuated and strongly immunogenic distinguishable vaccine candidate, a waaJ (a gene involved in the synthesis of lipopolysaccharide) and spiC (a virulence gene) double deletion Korean epidemic strain of S. enterica ser. Gallinarum (SG005) was constructed. Our results showed that the growth and biochemical characteristics were not altered by this double deletion. The double deletion strain contained dual markers. One was a bacteriological marker (rough phenotype) and the other was a serological marker helping distinguish infected chickens from vaccinated chickens. The double deletion strain showed good genetic stability and reduced resistance to environmental stresses in vitro; furthermore, it was extremely safe and highly avirulent in broilers. Single intramuscular or oral immunization of 7-day-old broilers with the double deletion strain could stimulate the body to produce antibody levels similar to the conventional vaccine strain SG9R. In addition, against a lethal wild-type challenge, it conferred effective protection that was comparable to that seen in the group vaccinated with SG9R. In conclusion, this double deletion strain may be an effective vaccine candidate for controlling S. enterica ser. Gallinarum infection in broilers.

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).

Ad26.COV2.S viral vector vaccine’s safety and immunogenicity: A review of literature

2021 ◽  
Author(s):  
Sherry Eskander
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Viral Vector ◽  
The Body ◽  
Effective Vaccine ◽  
Future Directions ◽  
Information Encoding ◽  
Vector Vaccine ◽  
High Risk Populations ◽  
Viral Vector Vaccine

COVID-19 is a respiratory infectious disease that spreads through droplets. This disease has brought immense changes that impacted all countries around the world and the healthcare system in many ways. Developing an effective vaccine has been a high priority and clinical trials are continuously conducted to improve their efficacy. There are two current competing forms of the vaccine: the first is mRNA vaccines, where they act as a carrier for immunological information encoding for the antigen (spike proteins) and induce an immune response without interacting with the genome. Although they have an effectiveness of 95%, they do require two doses to be fully effective. On the other hand, viral vector-based vaccines use a vector to deliver the genetic code for the antigen and, like a normal infection, uses the body cell’s machinery to produce more antigen, triggering an immune response.  Many clinical trials are being done to improve and evaluate its efficacy as this vaccine provides substantial potential advantages, one of which includes requiring only one dosage to be vaccinated to reach greater effectiveness in inducing antibody and CD4 T cells production. In consideration of the WHO SAGE Roadmap for vaccine prioritization, the aim of this study is to provide a review of the current literature and clinical trials being conducted on the viral vector vaccine Ad26.COV2.S’s safety and immunogenicity. In addition, it assesses potential future directions, implications and the substantial benefits towards the health care system and at-high-risk populations.

scholarly journals Vaccination of Macaques against Pathogenic Simian Immunodeficiency Virus with Venezuelan Equine Encephalitis Virus Replicon Particles

2000 ◽  
Vol 74 (1) ◽  
pp. 371-378 ◽  
Author(s):  
Nancy L. Davis ◽  
Ian J. Caley ◽  
Kevin W. Brown ◽  
Michael R. Betts ◽  
David M. Irlbeck ◽  
...  
Keyword(s):  
Viral Load ◽  
Simian Immunodeficiency Virus ◽  
Limit Of Detection ◽  
Rhesus Macaques ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Effective Vaccine ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Immunodeficiency Virus

ABSTRACT Vaccine vectors derived from Venezuelan equine encephalitis virus (VEE) that expressed simian immunodeficiency virus (SIV) immunogens were tested in rhesus macaques as part of the effort to design a safe and effective vaccine for human immunodeficiency virus. Immunization with VEE replicon particles induced both humoral and cellular immune responses. Four of four vaccinated animals were protected against disease for at least 16 months following intravenous challenge with a pathogenic SIV swarm, while two of four controls required euthanasia at 10 and 11 weeks. Vaccination reduced the mean peak viral load 100-fold. The plasma viral load was reduced to below the limit of detection (1,500 genome copies/ml) in one vaccinated animal between 6 and 16 weeks postchallenge and in another from week 6 through the last sampling time (40 weeks postchallenge). The extent of reduction in challenge virus replication was directly correlated with the strength of the immune response induced by the vectors, which suggests that vaccination was effective.

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