Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

Background: Several techniques are under investigation to improve the immunogenicity of HIV-1 DNA vaccine candidates. DNA vaccines are advantageous due to their ease of design, expression of multiple antigens, and safety. Methods: The HVTN 098 trial assessed the PENNVAX®-GP DNA vaccine (encoding HIV env, gag, pol) administered with or without plasmid IL-12 at 0-, 1-, 3-, and 6-month timepoints via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, adult participants. We report on safety, tolerability, and acceptability. Results: HVTN 098 enrolled 94 participants: 85 received PENNVAX®-GP and nine received placebo. Visual analog scale (VAS) pain scores immediately after each vaccination were lower in the ID/EP than in the IM/EP group (medians 4.1–4.6 vs. 6–6.5, p < 0.01). IM/EP participants reported greater pain and/or tenderness at the injection site. Most ID/EP participants had skin lesions such as scabs/eschars, scars, and pigmentation changes, which resolved within 6 months in 51% of participants (24/55). Eighty-two percent of IM/EP and 92% of ID/EP participant survey responses showed acceptable levels of discomfort. Conclusions: ID/EP and IM/EP are distinct experiences; however, HIV-1 DNA vaccination by either route was safe, tolerable and acceptable by most study participants.

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Immunogenicity of a novel DNA vaccine cassette expressing multiple human immunodeficiency virus (HIV-1) accessory genes

AIDS ◽

10.1097/00002030-200001070-00001 ◽

2000 ◽

Vol 14 (1) ◽

pp. 1-9 ◽

Cited By ~ 33

Author(s):

Velpandi Ayyavoo ◽

Sagar Kudchodkar ◽

Mathura P. Ramanathan ◽

Phong Le ◽

Karuppiah Muthumani ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Dna Vaccine ◽

Accessory Genes ◽

Immunodeficiency Virus ◽

Hiv 1

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Monkey Models of Tuberculosis: Lessons Learned

Infection and Immunity ◽

10.1128/iai.02850-14 ◽

2014 ◽

Vol 83 (3) ◽

pp. 852-862 ◽

Cited By ~ 45

Author(s):

Juliet C. Peña ◽

Wen-Zhe Ho

Keyword(s):

Mycobacterium Tuberculosis ◽

Animal Models ◽

Nonhuman Primates ◽

Lessons Learned ◽

Preclinical Testing ◽

Content Type ◽

Cynomolgus Macaques ◽

Drug Regimens

The use of animal models has been invaluable for studying the pathogenesis ofMycobacterium tuberculosisinfection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.

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Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1

Journal of General Virology ◽

10.1099/vir.0.80481-0 ◽

2005 ◽

Vol 86 (2) ◽

pp. 349-354 ◽

Cited By ~ 35

Author(s):

Eva K. L. Nordström ◽

Mattias N. E. Forsell ◽

Christina Barnfield ◽

Eivor Bonin ◽

Tomas Hanke ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Dna Vaccine ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Semliki Forest Virus ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

With the human immunodeficiency virus type 1 (HIV-1) epidemic expanding at increasing speed, development of a safe and effective vaccine remains a high priority. One of the most central vaccine platforms considered is plasmid DNA. However, high doses of DNA and several immunizations are typically needed to achieve detectable T-cell responses. In this study, a Semliki Forest virus replicon DNA vaccine designed for human clinical trials, DREP.HIVA, encoding an antigen that is currently being used in human trials in the context of a conventional DNA plasmid, pTHr.HIVA, was generated. It was shown that a single immunization of DREP.HIVA stimulated HIV-1-specific T-cell responses in mice, suggesting that the poor immunogenicity of conventional DNA vaccines may be enhanced by using viral replicon-based plasmid systems. The results presented here support the evaluation of Semliki Forest virus replicon DNA vaccines in non-human primates and in clinical studies.

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Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine

Vaccine ◽

10.1016/s0264-410x(02)00238-4 ◽

2002 ◽

Vol 20 (23-24) ◽

pp. 2857-2865 ◽

Cited By ~ 95

Author(s):

Y KOJIMA

Keyword(s):

Dna Vaccine ◽

Adjuvant Effect ◽

Cpg Motifs ◽

Hiv 1

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In-vitro and in-vivo Evaluation of Anti-asthmatic Activity of Eugenia jambolana bark

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00580 ◽

2021 ◽

pp. 3337-3342

Author(s):

Bhong Prabha N. ◽

Naikawade Nilofar. S. ◽

Mali Pratibha. R. ◽

Bindu Madhavi. S.

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Animal Models ◽

Aqueous Extract ◽

Guinea Pigs ◽

Bark Extract ◽

Eugenia Jambolana ◽

In Vivo Animal Models

Objectives: The present study designed to evaluate the Antiasthmatic activity of aqueous extract of bark of Eugenia Jambolana (AEEJ) on in vitro and in vivo animal models. Materials and methods: Different in vitro and in vivo animal models was used to study the anti asthmatic activity as isolated goat tracheal chain preparation, Acetylcholine and Histamine induced bronconstriction in guinea pigs, effect of drug extract on histamine release from mast cell was checked by clonidine-induced mast cell degranulation, and milk-induced eosinophilia and leukocytosis. Results: In-vitro study on goat tracheal chain preparation revealed that aqueous extract of Eugenia jambolana (AEEJ)bark exerted antagonistic effect on the histamine induced contraction. (P<0.05) The guinea pigs when exposed to 0.2% histamine aerosol showed signs of progressive dyspnoea leading to convulsions. AEEJ significantly prolonged the latent period of convulsions (PCT) as compared to control following the exposure of histamine (0.2%) aerosol (P<0.01). The observation of present study indicates aqueous extract of Eugenia jambolana shows significant inhibition of milk induced eosinophilia and leukocytosis. Group of animals pretreated with aqueous Eugenia jambolana bark extract showed significant reduction in degranulation of mast cells when challenged with clonidine. The prevention of degranulation process by the aqueous Eugenia jambolana bark extract (P<0.01) indicates a possible stabilizing effect on the mast cells, indicating mast cell stabilizing activity. Conclusions: Thus, AEEJ showed antihistaminic, mast cell stabilizing and protective in guinea pigs against histamine induced PCD, reduced eosinophilia and leukocytosis and hence possesses potential role in the treatment of asthma.

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Glycoprotein Ibα clustering induces macrophage-mediated platelet clearance in the liver

Thrombosis and Haemostasis ◽

10.1160/th14-03-0217 ◽

2015 ◽

Vol 113 (01) ◽

pp. 107-117 ◽

Cited By ~ 19

Author(s):

Na Ma ◽

Lili Zhao ◽

Cao Lijuan ◽

Yiwen Zhang ◽

Jie Zhang ◽

...

Keyword(s):

Platelet Aggregation ◽

Intravenous Injection ◽

Guinea Pigs ◽

Immune Thrombocytopenia ◽

Underlying Mechanism ◽

Therapeutic Strategies ◽

Integrin Αiibβ3 ◽

N Terminus ◽

Cynomolgus Macaques ◽

Independent Mechanism

SummaryMany immune thrombocytopenia (ITP) patients, particularly patients with anti-glycoprotein (GP) Ib-IX autoantibodies, do not respond to the conventional treatments such as splenectomy. However, the underlying mechanism remains unclear. Here we found that anti-GPIbα N-terminus antibody AN51, but not other anti-GPIbα antibodies (AK2, HIP1, VM16d, or WM23), induced GPIbα clustering that led to integrin αIIbβ3-dependent platelet aggregation. After intravenous injection, AN51 dose-dependently induced thrombocytopenia in guinea pigs, and the platelets were mainly removed by macrophages in the liver. N-acetyl-D-glucosamine, previously shown to inhibit integrin αMβ2-mediated phagocytosis of refrigerated platelets, dose-dependently inhibited AN51-induced platelet clearance. Furthermore, AN51 but not VM16d, induced rapid platelet clearance in the liver of cynomolgus macaques. Five of 22 chronic ITP patients had anti-GPIbα autoantibodies, and the autoantibodies from four of the five patients competed with AN51 for binding to platelets. These data indicate that GPIbα clustering induced by anti-GPIbα N-terminus antibody causes integrin αIIbβ3-dependent platelet aggregation, phagocytosis, and rapid platelet clearance in the liver. Our findings reveal a novel Fc-independent mechanism underlying the pathogenesis of ITP, and suggest new therapeutic strategies for ITP patients with anti-GPIbα autoantibodies.

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A Novel Tuberculosis DNA Vaccine in an HIV-1 p24 Protein Backbone Confers Protection against Mycobacterium tuberculosis and Simultaneously Elicits Robust Humoral and Cellular Responses to HIV-1

Clinical and Vaccine Immunology ◽

10.1128/cvi.05700-11 ◽

2012 ◽

Vol 19 (5) ◽

pp. 723-730 ◽

Cited By ~ 4

Author(s):

Xiaoman Li ◽

Wei Xu ◽

Sidong Xiong

Keyword(s):

Mycobacterium Tuberculosis ◽

T Cell ◽

Dna Vaccine ◽

Cellular Response ◽

Mycobacterial Infection ◽

T Cell Epitopes ◽

Content Type ◽

P24 Protein ◽

Elevated Frequency ◽

Hiv 1

ABSTRACTTuberculosis (TB) caused byMycobacterium tuberculosisremains a major infectious disease worldwide. Moreover, latentM. tuberculosisinfection is more likely to progress to active TB and eventually leads to death when HIV infection is involved. Thus, it is urgent to develop a novel TB vaccine with immunogenicity to bothM. tuberculosisand HIV. In this study, four uncharacterized T cell epitopes from MPT64, Ag85A, Ag85B, and TB10.4 antigens ofM. tuberculosiswere predicted, and HIV-1-derived p24, an immunodominant protein that can induce protective responses to HIV-1, was used as an immunogenic backbone.M. tuberculosisepitopes were incorporated separately into the gene backbone of p24, forming a pP24-Mtb DNA vaccine. We demonstrated that pP24-Mtb immunization induced a strongM. tuberculosis-specific cellular response as evidenced by T cell proliferation, cytotoxicity, and elevated frequency of gamma interferon (IFN-γ)-secreting T cells. Interestingly, a p24-specific cellular response and high levels of p24-specific IgG were also induced by pP24-Mtb immunization. When the protective effect was assessed after mycobacterial challenge, pP24-Mtb vaccination significantly reduced tissue bacterial loads and profoundly attenuated the mycobacterial infection-related lung inflammation and injury. Our findings demonstrated that the pP24-Mtb tuberculosis vaccine confers effective protection against mycobacterial challenge with simultaneously elicited robust immune responses to HIV-1, which may provide clues for developing novel vaccines to prevent dual infections.

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