A Macromolecular Multicomponent Peptide Vaccine Prepared Using the Glutaraldehyde Conjugation Method with Strong Immunogenicity for HIV-1

Hamajima, Kenji; Bukawa, Hiroki; Fukushima, Jun; Kawamoto, Susumu; Kaneko, Tamiko; Sekigawa, Kenichiro; Tanaka, Shun‐ichi; Tsukuda, Mamoru; Okuda, Kenji

doi:10.1006/clin.1995.1165

Cited by 25 publications

(13 citation statements)

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“…In another hand, significant antibody and cytotoxic responses have been induced at mucosal levels applying synthetic peptides along with adjuvants through mucosa (9,39). Other effective epitope-vaccine strategies have included branching peptide (20,24,29) and peptide chemically conjugated to a variety of carriers (18). Numerous HIV vaccine strategies, including epitopic peptide designs, have been focused in the V3 loop of gp120 HIV as a vaccine target.…”

Section: Introductionmentioning

confidence: 99%

Production of a Short Recombinant C4V3 HIV-1 Immunogen That Induces Strong Anti-HIV Responses by Systemic and Mucosal Routes Without the Need of Adjuvants

2006

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Synthetic peptides have been shown to evoke neutralizing and cytotoxic protective anti-HIV responses in mice and other animal models. Recent data support that C4V3 peptides can induce anti- V3 antibodies that neutralize primary isolates. Critical to the success of peptide-based vaccines is the development of strategies to augment their immunogenicity while reducing their large-scale production costs. Therefore, finding efficient and economical alternatives for the production of epitopic vaccines could have an impact on researches using such immunogens. Herein, we report the recombinant production and immunological characterization of a short polypeptide which carries the three relevant epitopes contained in a C4V3 peptide. This polypeptide, named rC4V3, was efficiently produced in E. coli, yielding more than 75 mg per culture liter. No major difficulties were found in the recovery, refolding and purification of this peptide; the latter facilitated by C-terminal inclusion of a histidine tag. The immunogenicity of this protein was studied by administering it intramuscularly or intranasally to mice and it demonstrated to be a strong elicitor of anti-HIV antibodies at systemic and mucosal compartments. Remarkably, such responses were attained with rC4V3 even without the need of adjuvants. We can conclude that this protein might be a promising tool for studies using epitope-based vaccine designs.

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Section: Introductionmentioning

confidence: 99%

Production of a Short Recombinant C4V3 HIV-1 Immunogen That Induces Strong Anti-HIV Responses by Systemic and Mucosal Routes Without the Need of Adjuvants

2006

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“…For example, immunization therapies [5,6] used for protection against AIDS and other infectious diseases are actually related to the delivery of protein vaccines; gene therapies for treatment of carcinoma, haemophilia [15,16] and scurvy all require the delivery of gene compounds; tissue engineering for organ repair and regeneration relies on the delivery of proteins and cells; and stem cell therapy [17], which is the most promising strategy to-date in treating any type of disease, is about the delivery of stem cells. It should be pointed out that among the 10000 different drugs presently available, only 120 of them are macromolecular drugs, a mere 1.2% occupancy.…”

Section: Significance Of Developing Bio-macromolecular Drugsmentioning

confidence: 99%

“…Although these delivery technologies have been successfully applied to enhance the therapeutic efficacy of the new chemical entities, they are still unable to overcome the poor cell permeability issue for macromolecular drugs. For this reason, all currently existing drug delivery systems for macromolecular compounds remained at the stage of delivering large drugs that could exert their therapeutic functions without the need to enter cells, such as insulin [19,29,30], hormones [28,31], vaccines [6] and tissue plasminogen activators (t-PA) [32] etc.…”

Section: Importance Of Developing Drug Delivery Systems (Dds)mentioning

confidence: 99%

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Developing macromolecular therapeutics: the future drug-of-choice

Dong

Gong

et al. 2010

Front. Chem. Eng. China

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Macromolecular drugs including peptides, proteins, antibodies, polysaccharides and nucleic acids have been widely used for therapy of major diseases such as carcinoma and AIDS as well as cardiovascular and neurodegenerative disorders among other medical conditions. Due to their unmatched properties of high selectivity and efficiency, macromolecular drugs have been recognized as the drug-of-choice of the future. Since worldwide progress on macromolecular therapeutics still remains in the infant stage and is therefore wide open for equalground competition, R&D related to macromolecular drugs should be considered as the main point of focus in China in setting up its strategic plans in pharmaceutical development. In this article, research strategies and drug delivery approaches that should be adopted to enhance the therapeutic effects of macromolecular drugs are reviewed. In addition, comments concerning how to implement such strategies to excel from competition in this challenging research field, such as the design of innovative and highly effective delivery systems of macromolecular drugs with self-owned intellectual property rights, are provided.

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“…We previously developed peptide vaccines for HIV-1 that were constructed from four V3 peptides13-16 and one Gag region peptide.17 However, it is difficult to induce a strong helper T cell type 1 (Thl) response with these vaccines unless appropriate adjuvants are also employed. 18 We have been developing an HIV-specific DNA vaccine candidate that is constructed from HIV-1 env and rev genes.1419 Immunization with this antigen resulted in substantial humoral and cell-mediated immune (CMI) responses to HIV-1 antigen.19 To achieve protective immunity against HIV-1 infection, the induction of a strong cytotoxic T lymphocyte (CTL) response has been shown to be important. 20 '21 To accomplish this, it is vital for cells to be capable of endogenous production of antigenic peptides.…”

Section: Introductionmentioning

confidence: 99%

Cationic Liposomes Are a Strong Adjuvant for a DNA Vaccine of Human Immunodeficiency Virus Type 1

Ishii¹,

Fukushima²,

Kaneko³

et al. 1997

AIDS Research and Human Retroviruses

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100

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Liposomes have been widely used to enhance the immune response. In the present investigation, we studied their in vivo immunomodulation of an HIV-1-specific DNA vaccine candidate (pCMV160/REV) constructed with the cytomegalovirus (CMV) promoter-conjugated HIV-1 env and rev DNA plasmids. By immunizing with pCMV160/REV and cationic liposomes through various routes (intramuscular, intraperitoneal, subcutaneous, intradermal, and intranasal), we induced higher levels of both antibody production and delayed-type hypersensitivity (DTH) than by using DNA vaccine alone. The HIV-1-specific cytotoxic T lymphocyte (CTL) activity was observed to be stronger on immunization with the DNA vaccine and cationic liposome combination. The intramuscular, intraperitoneal, and intranasal inoculation routes were more effective in inducing strong DTH and antibody responses than the subcutaneous and intradermal routes. Taken together, these results suggest that cationic liposomes can be highly effective when used with DNA vaccines and administered by various routes.

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A Macromolecular Multicomponent Peptide Vaccine Prepared Using the Glutaraldehyde Conjugation Method with Strong Immunogenicity for HIV-1

Cited by 25 publications

References 0 publications

Production of a Short Recombinant C4V3 HIV-1 Immunogen That Induces Strong Anti-HIV Responses by Systemic and Mucosal Routes Without the Need of Adjuvants

Production of a Short Recombinant C4V3 HIV-1 Immunogen That Induces Strong Anti-HIV Responses by Systemic and Mucosal Routes Without the Need of Adjuvants

Developing macromolecular therapeutics: the future drug-of-choice

Cationic Liposomes Are a Strong Adjuvant for a DNA Vaccine of Human Immunodeficiency Virus Type 1

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