Enhanced antibody response to liposome-associated protein antigens: preferential stimulation of IgG2a/b production

Phillips, Nigel C.; Emili, Andrew

doi:10.1016/0264-410x(92)90004-4

Cited by 47 publications

(17 citation statements)

References 30 publications

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“…Liposomes have a number of advantages a) they are biodegradable, non-toxic and immunologically inert, b) serve as carriers and depots of antigens enhancing the uptake and presentation of antigens by APC's, leading to efficient stimulation of the T cells (16), c) long lasting, high titre as well as high affinity functional antibodies can be achieved for antigens administered through various routes (17,18), d) cell mediated immunity can be induced (19), e) other adjuvants such as MPL, LPS and MDP analogs can be co-entrapped along with the antigen to further enhance the quality of the immune response (20), f) toxicity of antigens and adjuvants can be reduced or eliminated by entrapment in liposomes (21), g) liposomes can also be used to enhance the production of cytophilic antibodies viz. IgG2a/ IgG2b type (22), h) there are convincing reports to indicate that encapsulation inside the liposome in no way disturbs the native conformation (23)~…”

Section: Liposomesmentioning

confidence: 99%

New age adjuvants and delivery systems for subunit vaccines

Koduri

Manocha

Sabhnani

et al. 2000

Indian J Clin Biochem

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The dramatic advancements in the field of vaccinology has led to the formulation of chemically well defined vaccines composed of synthetic peptides and recombinant proteins derived from the immunologically dominant regions of the pathogens. Though these subunit vaccines are safer compared to the traditional vaccines they are known to be poorly immunogenic. This necessitates the use of adjuvants to enhance the immunogenicity of these vaccine formulations. The most common adjuvant for human use is alum. Research in the past has focused on the development of systemic immunity using conventional immunization protocols. In the present era, the emphasis is on the development and formulation of alternative adjuvants and delivery systems in generating systemic as well as mucosal immunity. This review mainly focuses on a variety of adjuvants (particulate as well as non-particulate) used with protective antigens of HIV, malaria, plague, leprosy using modified delivery vehicles. The experience of our laboratory and other researchers in this field clearly proves that these new age adjuvants and delivery systems undoubtedly generate enhanced immune response -both humoral and cell mediated. The choice of antigens, the nature of adjuvant used and the mode of delivery employed have a profound effect on the type of immune response generated. Besides the quantity, the quality of the antibodies generated also play a vital role in protection against these diseases. Some of the adjuvants and delivery systems used promoted high titre and affinity antibodies, which were shown to be cytophilic in nature, an important criteria in providing protection to the host. Thus the studies on these adjuvants/ delivery systems with respect to various infectious diseases indicate their active role in efficient modulation of immune response along with safety and permissiblity.

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Section: Liposomesmentioning

confidence: 99%

New age adjuvants and delivery systems for subunit vaccines

Koduri

Manocha

Sabhnani

et al. 2000

Indian J Clin Biochem

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“…Although alum adsorbed formulations are known to produce IgG1 isotype during primary response an additional IgG2a/2b response was stimulated. The entrapment of peptides in aqueous compartments of liposomes induces isotypes IgG2a and IgG2b [31] and the presence of adjuvant [Thr 1 MDP] and metabolizable saponins such as Quil A enhances IgG2a production [32]. IgG2a subclass immunoglobulins are important in the defense against virus infection in which opsonisation and complement mediated lysis of virus and destruction of virus-infected cells by ADCC may be of great importance.…”

Section: Discussionmentioning

confidence: 99%

Generating neutralizing antibodies, Th1 response and MHC non restricted immunogenicity of HIV-I env and gagpeptides in liposomes and ISCOMs with in-built adjuvanticity

Agrawal

Haq²,

Hanson

et al. 2003

J Immune Based Ther Vaccines

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For enhancing immunogenicity and develop vaccine strategies using peptide based constructs against HIV-1, a chimeric peptide containing V3 loop and transmembrane sequence of gp41 with two glycine motifs as spacer was constructed. The V3-gp41, gp41 peptide and p17 and p24 peptides separately or in a cocktail were entrapped with or without MA729 as an immunoadjuvant in liposomes or ISCOMs. The immunogenicity, antigen induced T-cell proliferation and cytokine profiles of various formulations were studied in four different inbred strains of mice of H-2 d , H-2 b , H-2 k and H-2 q haplotypes, keeping alum as a control adjuvant. Both liposomes and ISCOM preparations elicited high titer and long lasting antibody response (60 days and above). When compared to the alum formulation, the liposomes co-entrapped with MA729 produced high antibody levels, comparable with that induced by ISCOMs. Peptide in alum, liposomes and ISCOMs enhanced both antigen specific IgG2a and IgG2b isotypes and high T-cell stimulation index. Peptide formulations also induced antibodies with high affinity and in vitro neutralizated the formation of HIV-1 syncytia. T-cell supernatants contained high levels of IFN-γ and IL-2. Thus formulation in these adjuvants induced a predominant Th1 like response with MA729 as a versatile novel delivery vehicle for stimulating the appropriate arm of the immune response that can selectively modulate MHC class I or MHC class II response. The above peptide can be of wide vaccination interest as a means to improve immune responses to several other HIV-1 antigens and may serve as candidates for vaccine development.

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“…The incorporation of such antigens in delivery vehicles, e.g. egg PtdCho liposomes, usually results in the same fate except for an increase in overall antigen specific humoral immune response [3,[29][30][31]. However, delivery of the same exogenous antigen in cytosol of the antigen presenting cells can also induce a cytotoxic T lymphocyte response [6, 10,28,32].…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports on the application of liposomes, in relation to vaccine development, have demonstrated that liposomes may have the potential of being antigen carriers [1,2]. The major justification and rationale behind exploring the potential of liposomes as vehicles for vaccines resides in their striking tendency to be accumulated by the antigen‐presenting cells (APCs) through active endocytosis, both in vitro and in vivo [3,4]. However, the uptake of the liposomised antigen through endocytosis, eventually leads to the preferential stimulation of the humoral immune response, and poses a major hindrance in the generation of cytotoxic T lymphocytes (CTLs) against the exogenous antigens [5].…”

mentioning

confidence: 99%

Fusogenic potential of prokaryotic membrane lipids.

Ahmad

Masood

Owais

2001

European Journal of Biochemistry

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Development of protective immunity against many pathogens, particularly viruses, requires fine orchestration of both humoral‐ and cell mediated‐immunity. The immunization of animals with soluble antigens usually leads to the induction of humoral immune responses. In contrast, the activation of a cell‐mediated immune response against exogenous antigens has always been a challenge, requiring special strategies to expose them to the proteasome, a multifunctional protease complex in the cytosol of the target cells. The degradation of the protein by the cytosolic proteolytic system forms a cardinal step for the induction of cytotoxic T lymphocytes (CTLs). In the present study, we report that a potent primary CTL response against a soluble protein, ovalbumin, can be induced in mice by encapsulating it in the liposomes comprised of Escherichia coli membrane lipids. These lipids were shown to induce strong membrane–membrane fusion as evident from resonance energy transfer and content mixing assays. Furthermore, the fusion of these liposomes with living cells (J774 A1) was demonstrated to result in effective transfer of a fluorescent lipid probe to the plasma membrane of the cells. Moreover, ricin A, a protein synthesis inhibitor that does not cross plasma membrane, was demonstrated to gain access to the cytosol when it was encapsulated in these liposomes. Finally, the liposomes were demonstrated to behave like efficient vehicles for the in vivo delivery of the antigens to the target cells resulting in the elicitation of antigen reactive CD8+ T cell responses.

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Enhanced antibody response to liposome-associated protein antigens: preferential stimulation of IgG2a/b production

Cited by 47 publications

References 30 publications

New age adjuvants and delivery systems for subunit vaccines

New age adjuvants and delivery systems for subunit vaccines

Generating neutralizing antibodies, Th1 response and MHC non restricted immunogenicity of HIV-I env and gagpeptides in liposomes and ISCOMs with in-built adjuvanticity

Fusogenic potential of prokaryotic membrane lipids.

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