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

Ishii, Norihisa; Fukushima, Jun; Kaneko, Tamiko; Okada, Eiichi; Tani, Kenji; Tanaka, Shun‐ichi; Hamajima, Kenji; Xin, Ke-Qin; Kawamoto, Susumu; Koff, Wayne C.; Nishioka, Kusuya; Yasuda, Tatsuji; Okuda, Kenji

doi:10.1089/aid.1997.13.1421

Cited by 100 publications

(46 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These complexes combine activation of innate and ultimately adaptive immunity via TLR9 and non-TLR9 pathways coupled with antigen delivery (11,20,42,43). The use of cationic liposomes is thought to direct antigens to DC; enable entry into cells, specifically the endosome compartment; enhance entry into major histocompatibility complex class I pathways; and potentiate activation of innate immunity by TLR9 agonists, like plasmid DNA (11,18,22,44). Thus, the combination of cationic liposomes and plasmid DNA should improve both innate and adaptive immune responses.…”

Section: Discussionmentioning

confidence: 99%

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Bernstein

Cardin

Bravo

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

Development of a herpes simplex virus (HSV) vaccine is a priority because these infections are common. It appears that potent adjuvants will be required to augment the immune response to subunit HSV vaccines. Therefore, we evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant in a mouse model of genital herpes. Using a whole-virus vaccine (HVAC), we showed that the addition of CLDC improved antibody responses compared to vaccine alone. Most important, CLDC increased survival, reduced symptoms, and decreased vaginal virus replication compared to vaccine alone or vaccine administered with monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) following intravaginal challenge of mice. When CLDC was added to an HSV gD2 vaccine, it increased the amount of gamma interferon that was produced from splenocytes stimulated with gD2 compared to the amount produced with gD2 alone or with MPL-alum. The addition of CLDC to the gD2 vaccine also improved the outcome following vaginal HSV type 2 challenge compared to vaccine alone and was equivalent to vaccination with an MPL-alum adjuvant. CLDC appears to be a potent adjuvant for HSV vaccines and should be evaluated further.Herpes simplex virus type 1 (HSV-1) and HSV-2 are two members of the HSV family of alphaherpesviruses, which establish lifelong latent infection in sensory neurons and lead to chronic herpes disease. HSV-1 infection causes facial/ocular disease, while HSV-2 is the leading cause of genital herpes, although both viruses can be found at oral and genital sites. Indeed, the incidence of HSV-1 genital disease is increasing and approximates that of HSV-2 in certain countries (17). Approximately 45 million people in the United States (20 to 30%) have genital herpes infection, and new infections occur at a rate of 1 million per year (17,29). One of the most serious complications of genital herpes occurs when the virus is transmitted from mother to neonate. Infection of the neonate causes significant morbidity and mortality, even with proper antiviral therapy (25). Genital herpes infection also increases the risk of acquiring human immunodeficiency virus (HIV) infection and increases shedding of HIV in genital lesions (5, 40).HSV-2 infection induces both humoral and T-cell-mediated immunity; however, the mechanisms that contribute to longterm control of genital herpes are not understood and could be different from those that will protect against primary infection or disease. Studies from animal models of HSV infection and human studies indicate that high levels of neutralizing antibodies, innate immunity natural killer (NK) cells, interferon (IFN), and macrophages contribute to protection from HSV infection, but the major determinants of HSV protection are both CD8 ϩ and especially CD4 ϩ T cells (7,9,23,27,30,31). Clearance of virus from recurrent lesions is also more closely correlated to T-cell immunity. Thus, when a recurrent lesion occurs, mononuclear cells, primarily CD4 ϩ T cells, infiltrate the lesion as early as 2 days after formation and ...

show abstract

Section: Discussionmentioning

confidence: 99%

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Bernstein

Cardin

Bravo

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…Cationic liposomes have been shown previously to markedly potentiate activation of innate immunity by TLR9 agonists (bacterial DNA and CpG oligonucleotides) (17)(18)(19)(20)(21). The ability of cationic liposomes to potentiate activation of innate immunity by DNA is due to protection of the DNA from extracellular degradation and to enhanced entry of DNA into the endosomal compartment, where TLR9 is selectively expressed (19,22,23).…”

Section: S Timulation Of Innate Immunity Is Necessary For Generationmentioning

confidence: 99%

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Zaks

Jordan

Guth³

et al. 2006

The Journal of Immunology

227

187

View full text Add to dashboard Cite

Complexing TLR9 agonists such as plasmid DNA to cationic liposomes markedly potentiates their ability to activate innate immunity. We therefore reasoned that liposomes complexed with DNA or other TLR agonists could be used as effective vaccine adjuvants. To test this hypothesis, the vaccine adjuvant effects of liposomes complexed to TLR agonists were assessed in mice. We found that liposomes complexed to nucleic acids (liposome-Ag-nucleic acid complexes; LANAC) were particularly effective adjuvants for eliciting CD4+ and CD8+ T cell responses against peptide and protein Ags. Notably, LANAC containing TLR3 or TLR9 agonists effectively cross-primed CD8+ T cell responses against even low doses of protein Ags, and this effect was independent of CD4+ T cell help. Ag-specific CD8+ T cells elicited by LANAC adjuvants were functionally active and persisted for long periods of time in tissues. In a therapeutic tumor vaccine model, immunization with the melanoma peptide trp2 and LANAC adjuvant controlled the growth of established B16 melanoma tumors. In a prophylactic vaccine model, immunization with the Mycobacterium tuberculosis protein ESAT-6 with LANAC adjuvant elicited significant protective immunity against aerosol challenge with virulent M. tuberculosis. These results suggest that certain TLR agonists can be combined with cationic liposomes to produce uniquely effective vaccine adjuvants capable of eliciting strong T cell responses against protein and peptide Ags.

show abstract

“…The method of DNA transfection followed that previously reported (6,33,34). Briefly, 20 g of DNA plasmids were mixed with 40 g of Lipofectin in a polystyrene container.…”

Section: Purification Of Dcs and In Vitro Immunizationmentioning

confidence: 99%

“…However, adjuvants may be needed to enhance the immune response elicited by this DNA vaccine. Therefore, we and other groups have been studying the effects of multiple potential adjuvants, including cationic liposomes (6), Ribi adjuvant (7,8), vectamidin (9), QS21 (10), B7-2 (11), IL-2 (12), macrophage inflammatory protein-1␣ (13), IL-12 (11,14,15), TCA3 (16), and others (5).…”

mentioning

confidence: 99%

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

Kusakabe¹,

Xin²,

Katoh³

et al. 2000

The Journal of Immunology

Self Cite

120

View full text Add to dashboard Cite

The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c+, CD8+ cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100+ cells or both CD8+ and CD11c+ cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.

show abstract

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

Cited by 100 publications

References 44 publications

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

Contact Info

Product

Resources

About