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At least 19 recordsLinked to original sources
PubMed2000

Safety evaluation of recombinant cholera toxin B subunit produced by Bacillus brevis as a mucosal adjuvant.

Mucosal immune responses are known to play important roles in the establishment of protective immunity to microbial infections through mucosa. We examined the toxic effects of recombinant cholera toxin B subunit (rCTB) secreted by Gram-positive bacterium Bacillus brevis as a mucosal adjuvant. Incubation of guinea-pig peritoneal macrophages with cholera toxin (CT) or aluminium hydroxide gel (Al-gel) released a significantly higher activity of lactate dehydrogenase than did commercial natural CTB (CTB) or rCTB. Intraintestinal or intramuscular administration of CT, CTB or Al-gel caused severe histopathological reactions. CT also caused infiltration of neutrophils and irregular arrangement or partial loss of the respiratory epithelium. In addition, CT and CTB elicited vascular permeability-increasing effects. rCTB elicited no toxic effects to macrophages and no vascular permeability-increasing effects. Moreover, it is noticeable that no distinct local histopathological reactions were observed in the nasal cavity, the small-intestinal loop or the muscle given rCTB. These results suggest that, from a safety standpoint, rCTB is a useful candidate as mucosal vaccine adjuvant.

Adjuvants, Immunologic↗
PubMed1999

Bacterial toxins as mucosal adjuvants.

The use of mucosally administered killed bacteria or viruses as vaccines has a number of attractive features over the use of viable attenuated organisms, including safety, cost, storage and ease of delivery. Unfortunately, mucosally administered killed organisms are not usually effective as vaccines. The use of LT(R192G), a genetically detoxified derivative of LT, as a mucosal adjuvant enables the use of killed bacteria or viruses as vaccines by enhancing the overall humoral and cellular host immune response to these organisms, especially the Th1 arm of the immune response. With this adjuvant, protective responses equivalent to those elicited by live attenuated organisms can be achieved with killed organisms without the potential side effects. These findings have significant implications for vaccine development and further support the potential of LT(R192G) to function as a safe, effective adjuvant for mucosally administered vaccines. There are a number of unresolved issues regarding the use of LT and CT mutants as mucosal adjuvants. Both active-site and protease-site mutants of LT and CT have been constructed and adjuvanticity reported for these molecules in various animal models and with different antigens. There needs to be a side-by-side comparison of CT, LT, active-site mutants, protease-site mutants and recombinant B subunits regarding the ability to induce specific, targeted immunological outcomes as a function of route of immunization and nature of the co-administered antigen. Those side-by-side comparisons have not been carried out and there is a substantial body of evidence indicating that the outcomes may very well be different. With that information, vaccine strategies could be designed employing the optimum adjuvant/antigen formulation and route of administration for a variety of bacterial and viral pathogens. Also lacking is an understanding of the underlying cellular and intracellular signaling pathways activated by these different molecules and an understanding of the mechanisms of adjuvanticity at the cellular level. These are important issues because they take us beyond the phenomenological observations of "enhanced immunity" to a more clear understanding of the mechanisms of adjuvant activity.

Adjuvants, Immunologic↗
PubMed2001

The potential of CpG oligodeoxynucleotides as mucosal adjuvants.

The development of mucosal vaccines for humans has been hindered by the lack of safe yet effective mucosal adjuvants. Bacterial toxins are commonly used as adjuvants in animal models, but they are too toxic for use in humans. A novel class of adjuvant is CpG DNA, which contains unmethylated CpG dinucleotides in particular base contexts (CpG motifs). CpG DNA is most often coadministered with antigen in the form of synthetic oligodeoxynucleotides (CpG ODN), which are made with a nuclease-resistant phosphorothioate backbone. The vast majority of studies using CpG DNA as adjuvant have been with parenteral delivery; recently, however, mucosal immunization with CpG DNA as adjuvant has also been shown to induce both systemic (humoral and cellular) and mucosal antigen-specific immune responses. This review will highlight the recent uses of CpG DNA as an adjuvant at mucosal surfaces.

Adjuvants, Immunologic↗
PubMedDate not supplied

New generation of mucosal adjuvants for the induction of protective immunity.

Invasion of infectious agents through mucosal surfaces can be prevented by use of the common mucosal immune system (CMIS), which interconnects inductive tissues, including Peyer's patches (PPs) and nasopharyngeal-associated lymphoreticular tissue (NALT), and effector tissues of the intestinal and respiratory tracts. In order for the CMIS to induce maximal protective mucosal immunity, co-administration of mucosal adjuvant has been shown to be essential. When vaccine antigen is administered together with mucosal adjuvant, antigen-specific T-helper (Th) 1 and Th2 cells, cytotoxic T lymphocytes (CTLs) and IgA B cell responses are effectively induced by oral or nasal routes via the CMIS. In the early stages of induction of mucosal immune response, the uptake of orally or nasally administered antigens is achieved through a unique set of antigen-sampling cells, M cells located in follicle-associated epithelium (FAE) of inductive sites. After successful uptake, the antigens are immediately processed and presented by the underlying dendritic cells (DCs). Elucidation of the molecular/cellular characteristics of M cells and mucosal DCs will greatly facilitate the design of a new generation of effective mucosal adjuvants and of a vaccine delivery vehicle that maximises the use of the CMIS. Our recent efforts at mucosal vaccine development have focused on nasal administration of vaccine antigen together with nontoxic mutant-based or cytokine-/chemokine-based adjuvant for the induction of the protective immunity. To this end, a chimeric form of a nontoxic adjuvant combining the merits of mutant cholera toxin A subunit (mCT-A) and heat labile toxin B subunit (LT-B) was created as the second generation of detoxified toxin-based mucosal adjuvant. When a vaccine antigen was coexpressed together with an immune stimulatory/delivery molecule in crop seed, this edible vaccine is not only effective but also extremely practical in that it can be produced in huge quantities and preserved and shipped over long distances at room temperature without altering the quality of the vaccine. Because such qualities would greatly facilitate global vaccination, this new generation edible vaccines with a built-in adjuvant and/or M cell-targeted edible vaccine promises to be a powerful weapon for combating infectious diseases and bioterrorism.

Adjuvants, Immunologic↗
PubMed2002

The Mycoplasma-derived lipopeptide MALP-2 is a potent mucosal adjuvant.

The adjuvanticity of MALP-2, a 2-kDa synthetic lipopeptide with macrophage-stimulatory activity, was evaluated in BALB/c mice using beta-galactosidase (beta-gal) as model antigen. When co-administered with beta-gal by either the intranasal (i.n.) or i.p. route, MALP-2 (0.5 microg) was capable of increasing beta-gal-specific serum IgG titers by 675-3,560-fold (i.n.) and 64-128-fold (i.p.), respectively, as compared to immunization with beta-gal alone. Using MALP-2, almost maximal IgG responses were already stimulated following the first immunization, and the IgG titers were similar to those observed using 10 microg of cholera toxin B subunit (CTB) as adjuvant. The mucosal immune system was also effectively stimulated (p<0.05) when MALP-2 was administered by the i.n. route (36% and 23% of beta-gal-specific IgA in lung and vaginal lavages, respectively). The i.n. co-administration of MALP-2 stimulated a stronger cellular immune response than CTB, both in submandibular lymph nodes and spleen (p<0.05). The analysis of beta-gal-specific IgG isotypes and the profiles of cytokines secreted by in vitro re-stimulated cells showed that co-administration of MALP-2 triggered a dominant Th2-response pattern. A recruitment of B220(+) and MAC-1(+) cells with an up-regulated expression of MHC class I, CD80 (B7.1) and CD54 (ICAM-1) was observed in nasal associated lymphoid tissues from MALP-2 treated mice. Taken together, our results demonstrated that the synthetic lipopeptide MALP-2 represents a very promising adjuvant for the mucosal delivery of vaccine antigens.

Adjuvants, Immunologic↗
PubMed2004

Clostridium difficile toxin A carboxyl-terminus peptide lacking ADP-ribosyltransferase activity acts as a mucosal adjuvant.

The receptor binding domains of the most potent mucosal adjuvants, bacterial toxins and plant lectins, are organized in repeat units to recognize specific sugar residues. The lectin-like structure of the C-terminal region of Clostridium difficile toxin A prompted us to investigate the mucosal adjuvant properties of a nontoxigenic peptide corresponding to amino acids 2394 to 2706 (TxA(C314)). We compared TxA(C314) adjuvant activity to those of cholera toxin (CT) and Escherichia coli heat-labile enterotoxin subunit B (EtxB) coadministered orally or nasotracheally with poor peptide antigens (keyhole limpet hemocyanin [KLH] and hen egg lysozyme [HEL]). Levels of anti-KLH-specific serum immunoglobulin G (IgG) and IgA as well as that of mucosal IgA were significantly higher in animals immunized orally with TxA(C314) plus KLH than with KLH alone, CT plus KLH, or EtxB plus KLH. Following intranasal immunization with TxA(C314) plus HEL, levels of serum- and mucosa-specific antibodies were comparable to those induced by coadministering HEL with CT or EtxB. The TxA(C314) adjuvant effect following oral, but not intranasal, immunization was dose dependent. The analysis of the subclasses of anti-KLH-specific IgG isotypes and the cytokines released from splenocytes of immunized mice challenged in vitro with KLH indicates the induction of a mixed Th1/Th2-type immune response, with prevalence of the Th1 branch. We conclude that TxA(C314) enhances immune responses against mucosa-coadministered foreign antigens and represents a promising mucosal adjuvant, especially because its ability to stimulate mixed Th1/Th2 responses with a strong a Th1 component is extremely worthwhile against intracellular pathogens.

ADP Ribose Transferases↗
PubMed1998

Affinity purification of recombinant cholera toxin B subunit oligomer expressed in Bacillus brevis for potential human use as a mucosal adjuvant.

For use as a mucosal adjuvant for human vaccines, a simple method has been developed for the affinity purification of recombinant cholera toxin B subunit which had been expressed in a safe host, Bacillus brevis. Recombinant cholera toxin B subunit, adsorbed quantitatively to a D-galactose-agarose column, was eluted with an 0.1-0.4 M D-galactose gradient with a yield of > 90%. The cholera toxin B subunit preparation was similar to the native cholera toxin B subunit with respect to GM1 binding ability, remarkable stability of the pentamer, and the dissociation-reassociation property by shifting pHs. Cross-linking experiments with glutaraldehyde demonstrated that the pentameric form was predominant; tetrameric, trimeric, dimeric and monomeric forms were detected to a lesser extent, and additionally 10- and 15-mers were observed depending on the concentration of the cholera toxin B subunit.

Adjuvants, Immunologic↗
PubMed2000

Antipeptide antibody responses following intranasal immunization: effectiveness of mucosal adjuvants.

Toxicity is a major factor limiting the development and use of potent adjuvants for human mucosally delivered vaccines. Novel adjuvant formulations have recently become available, and in the present study two have been used for intranasal immunization with a synthetic peptide immunogen (MAP-M2). This peptide represents a multiple antigenic peptide containing multiple copies of a mimotope M2, a peptide mimic of a conformational epitope of the fusion protein of measles virus. MAP-M2 was administered intranasally to experimental animals together with synthetic oligodeoxynucleotides containing unmethylated CpG motifs with or without a mutant of wild-type enterotoxin of Escherichia coli (LTR72). The combination of the mutant toxin LTR72 and the CpG repeats, codelivered with a peptide immunogen, induced both local and systemic peptide- and pathogen-specific humoral and cellular immune responses comparable to those obtained after intranasal immunization with the wild-type toxin LT. In addition, this combination of adjuvants induced a predominantly immunoglobulin G2a antibody response. If both the LTR72 and CpG adjuvants are shown to be safe for use in humans, this particular combination would appear to have potential as an adjuvant for mucosally delivered vaccines in humans.

Adjuvants, Immunologic↗
PubMed2005

Mucosal adjuvants.

Vaccines delivered through mucosal surfaces are increasingly studied because of their properties to effectively induce mucosal immune responses, are cheap, easily administrable and suitable for mass vaccinations. The prospects of development of edible and intranasally administered (perhaps through nose drops or spray) vaccines are inciting a lot of interest and generating many studies. One major obstacle is to be able to induce systemic as well as mucosal responses to mucosal vaccines. Apart from immunizing with live viruses, this has proven to be a challenge and one way to overcome it is by using adjuvants. It is well established that toxins with little or no capacity to activate adenylate cyclase and thus lacking toxicity (CT or mutant Echerichia Coli labile toxin) improve performance of mucosal vaccines. Synthetic oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG) have synergistic action with other adjuvants, such as alum and CT when delivered mucosally. There are several other important candidates for use as mucosal adjuvants. The proinflammatory cytokines IL-1alpha, IL-12, and IL-18 can replace CT as a mucosal adjuvant for antibody induction and induce an increase of mucosal CTL's. IL-15 also has the potential to increase antigen-specific CTL activity when used as an adjuvant while IL-5 and IL-6 were shown to be able to markedly increase IgA reactivity to co-expressed heterologous antigen. Chemokines such as MCP-1 could also be used as potential adjuvant for mucosally administered DNA vaccines as it significantly increases mucosal IgA secretion and CTL responses.

Adjuvants, Immunologic↗
PubMed1995

The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins.

The bacterial enterotoxins, cholera toxin and the heat labile toxin of E. coli, are well known adjuvants for mucosal immune response. Their common A chain mediates the toxigenic mechanism by causing ADP ribosylation of G proteins and subsequent elevation of cAMP in target cells. A large IgA and IgG antibody response to admixed protein antigen (Ag) is the hallmark of these adjuvants and is clearly associated with the A chain activity. Expansion of Ag-specific B and T cells, alteration of T cell cytokine production, and changes in regulatory T cells have been reported as adjuvant mechanisms. The B chain derivatives of these toxins can also weakly enhance immune response, especially if covalently associated with Ag and used for nasophyrangeal immunization. Importantly, these toxins or their B chain derivatives can alter the normal immune regulation that produces oral tolerance. This indicates that they modulate mechanisms operative between the mucosal and systemic immune systems. There are some discrepancies between in vitro models of CT or LT activity and in vivo manifestations of their adjuvant activities. Interpretation of current data regarding in vivo mechanism is hampered by an incomplete understanding of how mucosal B and T cells can interact with systemic lymphoid tissue and vice versa. More important, there is no clear understanding of the early effects of the toxins on the local (and draining) mucosal lymphoid tissues. This is especially true in the critical areas of antigen presentation, T and B cell activation, and cytokine production.

Adenosine Diphosphate Ribose↗
PubMed2001

The identification of plant lectins with mucosal adjuvant activity.

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic.

Adjuvants, Immunologic↗
PubMed1996

Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant.

Immunization of the female reproductive tract is important for protection against sexually transmitted diseases and other pathogens of the reproductive tract. However, intravaginal immunization with soluble antigens generally does not induce high levels of secretory immunoglobulin A (IgA). We recently developed safe mucosal adjuvants by genetically detoxifying Escherichia coli heat-labile enterotoxin, a molecule with a strong mucosal adjuvant activity, and here we describe the use of the nontoxic mutant LTK63 to induce a response in the mouse vagina against ovalbumin (Ova). We compared intravaginal and intranasal routes of immunization for induction of systemic and vaginal responses against LTK63 and Ova. We found that LTK63 is a potent mucosal immunogen when given by either the intravaginal or intranasal route. It induces a strong systemic antibody response and IgG and long-lasting IgA in the vagina. The appearance of vaginal IgA is delayed in the intranasally immunized mice, but the levels of vaginal anti-LTK63 IgA after repeated immunizations are higher in the intranasally immunized mice than in the intravaginally immunized mice. LTK63 also acts as a mucosal adjuvant, inducing a serum response against Ova, when given by both the intravaginal and intranasal routes. However, vaginal IgA against Ova is stimulated more efficiently when LTK63 and antigen are given intranasally. In conclusion, our results demonstrate that LTK63 can be used as a mucosal adjuvant to induce antigen-specific antibodies in vaginal secretions and show that the intranasal route of immunization is the most effective for this purpose.

Animals↗
PubMed2001

Genetically manipulated bacterial toxin as a new generation mucosal adjuvant.

Cholera toxin (CT) and heat-labile toxin (LT) of Escherichia coli act as adjuvants for the enhancement of mucosal and serum antibody (Ab) responses to mucosally co-administered protein antigen (Ag). Both LT and CT induce B7-2 expression on antigen-presenting cells (APCs) for subsequent co-stimulatory signalling to CD4+ T cells. CT directly affects CD4+ T cells activated via the TCR-CD3 complex with selective inhibition of Th1 responses whereas LT maintains Th1 cytokine responses with inhibition of interleukin (IL)-4 production. Interestingly, while CT failed to induce mucosal adjuvant activity in the absence of IL-4, LT did so. Nontoxic mutant (m)CTs (S61F and E112K) retain adjuvant properties by inducing CD4+ Th2 cells, which provided effective help for the Ag-specific mucosal immunoglobulin (Ig)A, as well as serum IgG1, IgE and IgA Ab responses. The mCT E112K has been shown to exhibit two distinct mechanisms for its adjuvanticity. Firstly, mCT enhanced the B7-2 expression of APCs. Secondly, this nontoxic CT derivative directly affected CD4+ T cells and selectively inhibited Th1 cytokine responses. Thus, several lines of evidence indicate that enzyme activity can be separated from adjuvant properties of CT and this offers promise for the development of safe delivery of vaccines for mucosal IgA responses.

Adjuvants, Immunologic↗
PubMed2000

Immunostimulatory sequence oligodeoxynucleotide: A novel mucosal adjuvant.

The majority of infectious agents enter the body via mucosal surfaces. Therefore, there is great interest in developing vaccination strategies that lead to mucosal immunity. However, to generate strong mucosal immune responses to nonreplicating immunogens, mucosal delivery with an adjuvant is required, and no safe and effective mucosal adjuvants are presently available for use in humans. Recently, immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) has been shown to be a potent mucosal adjuvant. Intranasal (i.n.) delivery of antigen with ISS-ODN elicits a secretory IgA response both locally in respiratory secretions and distally in intestinal and vaginal secretions. In this regard, ISS-ODN has been shown to be as effective as cholera toxin (CT), but unlike CT, ISS-ODN has not been shown to have significant toxicity. Furthermore, i.n. antigen/ISS-ODN coimmunization induces a strong Th(1)-biased systemic immune response with cytotoxic T lymphocyte activity. These observations suggest that ISS-ODN would be an ideal mucosal adjuvant for development of vaccines against mucosal pathogens.

Adjuvants, Immunologic↗
PubMed2003

An enzymatically active a domain is required for cholera-like enterotoxins to induce a long-lived blockade on the induction of oral tolerance: new method for screening mucosal adjuvants.

The cholera-like enterotoxins (CLETS), cholera toxin (CT) and Escherichia coli heat-labile toxin (LT), are powerful mucosal adjuvants. Here we show that these toxins also induce a long-lived blockade (of at least 6 months) on the induction of oral tolerance when they are coadministered with the antigen ovalbumin. Strikingly, only enzymatically active CLETS induced this blockade on the induction of oral tolerance. In this regard, the enzymatically inactive mutants of CT and LT, CTK63 and LTK63, and their recombinant B pentamers, rCTB and rLTB, failed to block the induction of oral tolerance, demonstrating a stringent requirement for an enzymatically active A domain in this phenomenon. Together with the results of other recent studies, these results indicate that the enzymatic activity of CLETS, most likely cyclic AMP elevation, is responsible for their adjuvant effects. The results of this study also indicate that measuring the ability of putative mucosal adjuvants to block the induction of oral tolerance may be a superior method for measuring mucosal adjuvanticity.

Adjuvants, Immunologic↗
PubMed2002

Partial protection against experimental vaginal candidiasis after mucosal vaccination with heat-killed Candida albicans and the mucosal adjuvant LT(R192G).

The effectiveness of a mucosal vaccine composed of heat-killed Candida albicans (HK-CA) or C. albicans culture filtrate (CaCF) in conjunction with the mucosal adjuvant LT(R192G) against vulvovaginal candidiasis was examined in an estrogen-dependent murine model. Mice vaccinated intranasally with HK-CA + LT(R192G) exhibited a significant but short-lived protection accompanied by a vigorous delayed-type hypersensitivity response as well as high titers of circulating C. albicans-specific antibodies. Surprisingly, the levels of antigen-specific antibodies in the vaginal secretions of protected mice were negligible and no correlates of vaginal-associated Type 1 or Type 2 cytokines were observed. Vaginal priming with C. albicans before vaccination did not alter the protective outcome. Immunization with CaCF + LT(R192G) induced a discrete level of protection when administered intrarectally but not intranasally. These results suggest that mucosal vaccination can afford partial protection against vulvovaginal candidiasis, but the precise immune mechanisms responsible for protection are complex and as yet, not well understood.

Adjuvants, Immunologic↗
PubMed2001

Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants.

Most vaccines are still delivered by injection. Mucosal vaccination would increase compliance and decrease the risk of spread of infectious diseases due to contaminated syringes. However, most vaccines are unable to induce immune responses when administered mucosally, and require the use of strong adjuvant on effective delivery systems. Cholera toxin (CT) and Escherichia coli enterotoxin (LT) are powerful mucosal adjuvants when co-administered with soluble antigens. However, their use in humans is hampered by their extremely high toxicity. During the past few years, site-directed mutagenesis has permitted the generation of LT and CT mutants fully non toxic or with dramatically reduced toxicity, which still retain their strong adjuvanticity at the mucosal level. Among these mutants, are LTK63 (serine-to-lysine substitution at position 63 in the A subunit) and LTR72 (alanine-to-arginine substitution at position 72 in the A subunit). The first is fully non toxic, whereas the latter retains some residual enzymatic activity. Both of them are extremely active as mucosal adjuvants, being able to induce very high titers of antibodies specific for the antigen with which they are co-administered. Both mutants have now been tested as mucosal adjuvants in different animal species using a wide variety of antigens. Interestingly, mucosal delivery (nasal or oral) of antigens together with LTK63 or LTR72 mutants also conferred protection against challenge in appropriate animal models (e.g. tetanus, Helicobacter pylori, pertussis, pneumococci, influenza, etc). In conclusion, these LTK63 and LTR72 mutants are safe adjuvants to enhance the immunogenicity of vaccines at the mucosal level, and will be tested soon in humans.

Adjuvants, Immunologic↗
PubMed2000

Effectiveness of intranasal immunization with HIV-gp160 and an HIV-1 env CTL epitope peptide (E7) in combination with the mucosal adjuvant LT(R192G).

LT(R192G) is a novel mucosal adjuvant that induces protective immunity when co-administered with certain whole inactivated bacteria or viruses or with subunits of relevant virulence determinants from these pathogens. LT(R192G) stimulates antigen-specific humoral and cellular immune responses, both systemically and in mucosal compartments, and is safe and nontoxic at adjuvant effective doses. Intranasal (IN) immunization of mice with LT(R192G) in conjunction with oligomeric HIV-1 gp160 elevates antigen-specific systemic and mucosal IgG and IgA production and Th1- and Th2-type cytokine responses. Isotype characterization of induced IgG reveals that gp160 alone fails to stimulate IgG2a responses in the absence of adjuvant. Both IgG1 and IgG2a are induced by immunization in the presence of LT(R192G). Additionally, intranasal immunization with a 15-amino acid peptide corresponding to an HIV-1 Env CTL determinant and LT(R192G) induces systemic, peptide-specific CTL activity and Th1 and Th2 cytokine responses that are absent when the adjuvant is excluded from the immunizations. These studies show that LT(R192G) quantitatively and qualitatively enhances cellular and humoral HIV-specific immune responses and that this adjuvant may offer significant advantages toward vaccine development against HIV.

AIDS Vaccines↗