双价志贺菌苗灌胃免疫小鼠后肠粘膜的免疫应答

为了观察两株福氏、宋内双价志贺菌苗 (Ipa ,Ipa+ )免疫后所引起的肠粘膜诱导部位的免疫应答及为研制有效腹泻疫苗提供理论基础。应用小鼠灌胃免疫为模型 ,以间接免疫荧光法和BA ELISPOT方法 ,检测了肠粘膜相关淋巴组织 (gutasso ciatedlymphoidtissues ,GALT )中诱导部位派伊尔小结 (Payer’spatches ,PP )、肠系膜淋巴结 (mesentericlymphoidnode ,MLN )T淋巴细胞亚群和特异性抗体分泌细胞的变化 (ASC )及小肠局部和系统的特异性抗体变化。发现两株双价菌苗株均可引起肠粘膜GALT诱导部位CD4+ 淋巴细胞亚群、抗体分泌细胞明显升高 ;同时局部及血清中特异性抗体明显升高。说明双价志贺菌苗灌胃免疫小鼠后 ,诱导部位的免疫应答早期以体液免疫为主 ,灌胃不仅可诱导局部特异性抗体免疫应答也可诱导系统的抗体免疫应答。     

STAg和霍乱毒素不同程序滴鼻免疫小鼠诱导抗弓形虫作用

目的观察弓形虫可溶性速殖子抗原（soluble tachyzoite antigen，STAg）和霍乱毒素（cholera toxin，CT）佐剂不同程序滴鼻免疫小鼠诱导的抗弓形虫感染能力，确定STAg和CT滴鼻免疫的最佳程序。方法BALB／c小鼠随机分为3组：1次、2次和3次免疫组，用20μgSTAg＋1μgCT／只分别滴鼻免疫1次，2次或3次，前2次间隔2周，末次间隔1周。末次免疫后第14天，用4×10^4个速殖子／只灌胃攻击所有小鼠，观察小鼠健康及死亡情况，攻击后第30天处死，ELISA法检测血清IgG和粪便IgA，计数肝、脑组织内弓形虫速殖子，分离并计数派伊尔结（Peyer＇s patches，PP）和脾淋巴细胞数。结果2次和3次免疫组小鼠存活率明显高于1次免疫组（P〈0．05），肝、脑组织内虫荷显著低于1次免疫组（P〈0．001），血清IgG和粪便IgA高于1次免疫组，PP和脾淋巴细胞数无显著性变化。结论STAg和CT佐剂滴鼻免疫2次或3次能有效诱导小鼠抗弓形虫感染。     

Prime-Boost Immunization of Codon Optimized HIV-1 CRF01_AE Gag in BCG with Recombinant Vaccinia Virus Elicits MHC Class I and II Immune Responses in Mice

The HIV-1 CRF01_AE gag gene was modified by codon restriction for Mycobacterium spp. and transformed into BCG; and it was designated as rBCG/codon optimized gagE. This produced 11 fold higher HIV-1 gag protein expression than the recombinant native gene rBCG/HIV-1gagE. In mice, CTL activity could be induced either by a single immunization of the codon optimized construct or by using it as a priming antigen in the prime-boost modality with recombinant Vaccinia virus expressing native HIV-1 gag. Specific secreted cytokine responses were also investigated. Only when rBCG gag was codon optimized did the prime-boost immunization produce significantly enhanced IFN-γ and IL-2 secretion indicating recognition via CD4+ and CD8+ T cells, and these responses seemed to be codon optimized immunogen dose-responsive. On contrary, the prime-boost vaccination using an equal amount of native rBCG/HIV-1gagE instead, or a single rBCG/codon optimized gagE immunization, had no similar effect on the cytokine secretion. These findings suggest that the use of recombinant codon BCG construct with recombinant Vaccinia virus encoding CRF01_AE gag as the prime-boost HIV vaccine candidate, will induce CD4+ Th1 and CD8+ T cell cytokine secretions in addition to enhancing CD8+ CTL response.     

Cross-Reactive Immune Responses Against Mycobacterium bovis BCG in Mice Infected with Non-Tuberculous Mycobacteria Belonging to the MAIS-Group

Two bacillus Calmette–Guérin (BCG)-susceptible mouse strains, BALB/c and C57BL/6, were infected intravenously with Mycobacterium intracellulare , M. avium or M. scrofulaceum and monitored during 3 months for mycobacterial replication and antibody and Th1-type cytokine production in response to cytoplasmic and secreted antigens from M. bovis BCG. Whereas initial colony-forming unit (CFU) counts of M. intracellulare and M. avium were higher in lungs than in spleen, the opposite was observed for M. scrofulaceum . Mycobacterium intracellulare was the most virulent species and its replication could not be controlled in either mouse strain. It also induced the strongest antibody response. Mycobacterium avium was eliminated in both mouse strains and M. scrofulaceum finally was eliminated in C57BL/6 but multiplied in spleen from BALB/c mice. Significant sustained interleukin-2 and interferon-γ production towards BCG antigens was only found in M. scrofulaceum infection. As in BCG-vaccination, M. scrofulaceum -infected C57BL/6 mice demonstrated a higher response towards whole BCG culture filtrate, BCG extract and purified antigen 85 complex (Ag85) from BCG than did BALB/c mice. The data suggest that the presence of M. scrofulaceum in the environment may possibly interfere in genetically predisposed subjects with BCG vaccine and its protective efficacy against M. tuberculosis .     

Evaluation of Immune Responses in Mice after DNA Immunization with Putative Toxoplasma gondii Calcium-Dependent Protein Kinase 5

Toxoplasma gondii can cause serious public health problems and economic losses worldwide. Calcium-dependent protein kinases (CDPKs) are key mediators of T. gondii signaling pathways and are implicated as important virulence factors. In the present study, we cloned a novel T. gondii CDPK gene, named TgCDPK5, and constructed the eukaryotic expression vector pVAX-CDPK5. Then, we evaluated the immune protection induced by pVAX-CDPK5 in Kunming mice. After injection of pVAX-CDPK5 intramuscularly, immune responses, determined with lymphoproliferative assays and cytokine and antibody measurements, were monitored, and mouse survival times and brain cyst formation were evaluated following challenges with the T. gondii RH strain (genotype I) and the PRU strain (genotype II). pVAX-CDPK5 effectively induced immune responses with increased specific antibodies, a predominance of IgG2a production, and a strong lymphocyte proliferative response. The levels of gamma interferon (IFN-γ), interleukin 2 (IL-2), and IL-12(p70) and the percentages of CD3⁺ CD4⁺ and CD3⁺ CD8⁺ cells in mice vaccinated with pVAX-CDPK5 were significantly increased. However, IL-4 and IL-10 were not produced in the vaccinated mice. These results demonstrate that pVAX-CDPK5 can elicit strong humoral and cellular Th1 immune responses. The survival time of immunized mice challenged with the T. gondii RH strain (8.67 ± 4.34 days) was slightly, but not significantly, longer than that in the control groups within 7 days (P > 0.05). The numbers of brain cysts in the mice in the pVAX-CDPK5 group were reduced by ∼40% compared with those in the control groups (P < 0.05), which provides a foundation for the further development of effective subunit vaccines against T. gondii.     

口服幽门螺杆菌疫苗后小鼠粘膜免疫应答研究

为观测幽门螺杆菌 (Hp )全菌抗原和粘膜佐剂LT口服免疫Balb/c小鼠后的粘膜免疫应答 ,采用ELISPOT和ELISA法分析免疫小鼠胃粘膜、派伊尔小结 (PP )抗原特异性抗体分泌细胞和小肠粘液唾液sIgA抗体。结果表明抗原免疫组、抗原 +佐剂组胃粘膜、PP抗原特异性sIgA ASC、IgG ASC数量明显增加 ,尤以sIgA ASC为甚 ,并且抗原 +佐剂组明显高于单纯抗原组和对照组 ;小肠粘液唾液特异sIgA水平两免疫组均明显高于对照组 ,提示口服免疫可有效诱导粘膜免疫应答 ,局部特异sIgA在抗Hp感染中具有重要作用     

Immunization with Single Oral Dose of Alginate‐Encapsulated BCG Elicits Effective and Long‐Lasting Mucosal Immune Responses

Effective vaccination against pathogens, which enter the body through mucosal surfaces, requires the induction of both mucosal and systemic immune responses. Here, mucosal as well as systemic immune responses in the lung and spleen of BALB/c mice which were orally vaccinated with a single dose of alginate‐encapsulated bacille Calmette–Guerin (BCG) were evaluated. Twenty weeks after immunization, the vaccinated mice were challenged intranasally with BCG. Twelve weeks after immunization and 5 weeks after challenge, the immune responses were evaluated. Moreover, immune responses were compared with those of mice that were vaccinated with free BCG by subcutaneous (sc) and oral routes. Twelve weeks after the immunization, serum IgG level was higher in the sc‐immunized mice, while serum IgA level was higher in the orally immunized mice with encapsulated BCG. Significant productions of both IgG and IgA were only detected in lungs of mice orally immunized with encapsulated BCG. Proliferative and delayed‐type hypersensitivity responses and IFN‐γ production were significantly higher in mice immunized orally with encapsulated BCG, compared to mice immunized orally with free BCG. After challenge, the levels of IFN‐γ were comparable between sc‐immunized mice with free BCG and orally immunized with encapsulated BCG; however, significantly less IL‐4 was detected in mice which had received encapsulated BCG via oral route. Moreover, significant control of the bacilli growth in the lung of the immunized mice after intranasal challenge with BCG was documented in mice vaccinated with encapsulated BCG. These results suggest that oral immunization with alginate‐encapsulated BCG is an effective mean of inducing mucosal and systemic specific immune responses.     

Receptor-Dependent Immune Responses in Pigs after Oral Immunization with F4 Fimbriae

F4 receptor-positive (F4R⁺) and F4 receptor-negative (F4R⁻) pigs were orally vaccinated with purified F4 fimbriae of enterotoxigenic Escherichia coli (ETEC). Serum immunoglobulin G (IgG) and IgA responses were readily detected in F4R⁺ animals, whereas immune responses were not detected in F4R⁻ animals. Even after a subsequent oral infection with virulent F4⁺ ETEC and a booster immunization with F4, the F4R⁻ animals remained F4 seronegative whereas the unvaccinated F4R⁺ pigs exhibited clear IgA and IgG responses. These results clearly demonstrate that F4Rs are a prerequisite for an immune response following oral immunization. Furthermore, indications that oral F4 vaccination can induce mucosal protection were obtained, since the experimental ETEC infection did not induce a systemic booster response or fecal ETEC excretion in orally vaccinated F4R⁺ pigs, in contrast to the clear immune response and ETEC excretion of unvaccinated F4R⁺ animals. F4-specific IgA antibodies could be found in the feces of the vaccinated F4R⁺ pigs. They are secreted at the intestinal mucosal surface and appear to prevent ETEC infection. The F4R-dependent induction of a mucosal immune response can be used as a model to better understand mucosal immunization and mucosal immune responses and can contribute to the development of oral vaccines in veterinary as well as in human medicine.     

双价志贺疫苗滴鼻免疫小鼠后粘膜免疫与系统免疫应答持续时间的观察

本文探讨双价志贺疫苗滴鼻免疫小鼠一段时间后,粘膜免疫和系统免疫应答的变化。将BALB/c小鼠随机分为三组,每组30只。PBS、FSM-2117和FS-5416(菌量为5×10~6、1×10~7、4×10~7和4×10~7CFU/只/次)经滴鼻途径免疫小鼠。间隔2周,4次免疫后7、30和90d活杀,收集鼻咽、肺、肠、生殖道冲洗液和血清。采用ELISA法检测其中特异性抗福氏、宋内LPSIgA和IgG。结果是两株疫苗经鼻内免疫后,诱发鼻咽、肺、胃肠道和生殖道等不同粘膜部位及血清中特异性抗福氏、宋内LPSIgA、IgG的显著增加(P<0.01)。特异性抗体水平虽然在免疫后30、90d明显下降,但仍明显高于PBS对照组水平。故认为两株双价志贺疫苗滴鼻免疫小鼠后能有效诱导粘膜免疫和系统免疫应答,并持续较长时间。     

Enteric Immunization with Live Adenovirus Type 21 Vaccine II. Systemic and Local Immune Responses Following Immunization

Studies of the immunologic responses following administration of a live, enteric-coated adenovirus (ADV) type 21 vaccine showed that nine of ten vaccinees and none of five controls developed neutralizing antibody. Antibody activity of serum and secretory immunoglobulins was assayed by using a (14)C-labeled ADV-21 antigen in a radioimmunodiffusion system. Increases in immunoglobulin M, A and G (IgM, IgA, IgG) activity were detected in sera from vaccinees but not in those from controls. IgA copro antibody activity was also shown in vaccinees but not in controls. Nasal secretions showed no detectable IgA antibody responses by this method. These studies show marked differences in serum and local IgA antibody activity in induced enteric ADV infection compared to previously reported responses after natural infection. The protective role of secretory IgA in adenovirus infections is obscure. However, absence of nasal IgA responses may indicate that protection against disease with enteric ADV vaccines depends primarily upon humoral antibody.     

Cell-Mediated Immune Responses in Four-Year-Old Children after Primary Immunization with Acellular Pertussis Vaccines

Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) were assessed in 48-month-old recipients of acellular pertussis [aP] vaccines (either from Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and compared to CMI responses to the same antigens at 7 months of age, i.e., 1 month after completion of the primary immunization cycle. None of the children enrolled in this study received any booster of pertussis vaccines or was affected by pertussis during the whole follow-up period. Overall, around 75% of 4-year-old children showed a CMI-positive response to at least one B. pertussis antigen, independently of the type of aP vaccine received, and the proportion of CMI responders were at least equal at 48 and 7 months of age. However, longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary immunization became negative at 48 months of age. This loss was more than compensated for by conversion to positive CMI responses, ranging from 36% against FHA to 69% against PRN, in other children who were CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and 48 months of age. In particular, the frequency of seropositivity to PRN and FHA (but not to PT) was roughly three times higher in CMI converters than in nonconverters. The acquisition of CMI response to B. pertussis antigens in 48-month-old children was not associated with a greater frequency of coughing episodes lasting >/=7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that vaccination-induced systemic CMI may wane by 4 years of age but may be acquired or naturally boosted by symptomless or minor clinical infection by B. pertussis. This might explain, at least in part, the persistence of protection against typical pertussis in aP vaccine recipients despite a substantial waning of both Ab and CMI responses induced by the primary immunization.     

Anti-Sperm Antibodies in Female Mice: Responses Following Intrauterine Immunization

PROBLEM: The goal of this study was to measure anti-sperm antibodies in serum following intraluminal uterine immunization and to compare this with the formation of antibodies following intraperitoneal (i.p.) or anal immunization. METHOD: Mice were immunized with human sperm, and antibody was measured using an indirect immunobead assay. RESULTS: High levels of anti-sperm antibodies could be measured following intrauterine immunization and i.p. immunization. Anal immunization resulted in lower levels of antibody formation. Antibody formation after intrauterine immunization was less consistent following transcervical insertion than following needle insertion of sperm. CONCLUSION: The data suggest that intrauterine immunization can result in anti-sperm antibody formation under some conditions.     

Cell-Mediated Immune Responses of Preleukemic AKR Mice

Splenic lymphocytes from preleukemic AKR mice are capable of participating in various cell-mediated immune responses. Spleen cells from AKR mice aged 1 to 10 months produced a significant graft-versus-host reaction when injected into 8-day-old AKR × C57Bl/6 F₁ hybrids. Splenic lymphocytes from similarly aged mice were also capable of responding to allogenic stimulation in a mixed lymphocyte reaction. AKR mice aged 1 to 10 months developed a contact sensitivity response to picryl chloride. It was concluded that mice of this high-leukemic strain have a competent cell-mediated immune system and there is no depression of immunity during the preleukemic period.     

Immune Responses of the Protein-Deficient Guinea Pig to BCG Vaccination

Two groups of guinea pigs were maintained on high-protein and low-protein diets and immunized with intradermal BCG. Protein deficiency was accompanied by marked inhibition of local and systemic immune responses: a) The BCG nodule was poorly formed. There was marked delay and deficiency in the mobilization of macrophages. b) The draining lymph node was atrophic and showed little or no proliferation of lymphoid cells in the paracortical area. Macrophage accumulation occurred late but became diffuse and marked, in contrast to its consistent scarcity in the BCG nodule. c) In either location epithelioid cell transformation was retarded. Well-formed mature epithelioid cell granulomas were not seen. d) Bacilli persisted for a long time in the skin and lymph node lesions, e) Tuberculin sensitivity was greatly impaired in one-fifth of animals and absent in others. These findings were suggestive of macrophage dysfunction and depression of cell-mediated immunity to BCG in the protein-deficient guinea pig.     

Altered Immune Responses in Mice with Concomitant Schistosoma mansoni and Plasmodium chabaudi Infections

Mixed parasitic infections are common in many parts of the world. However, little is known about how concurrent infections affect the immunity to and/or pathogenesis of each other. Protection and elimination of blood-stage Plasmodium chabaudi chabaudi AS in resistant mice are characterized by a sequential activation of CD4⁺ Th1 and Th2 cells. The patent egg-laying stage of the murine model of Schistosoma mansoni is associated with a strong Th2 response to both Schistosoma and unrelated antigens. In this study, we investigated how infection of mice with S. mansoni would affect the immune response to and pathogenesis of a P. chabaudi infection. C57BL/6 mice infected with S. mansoni for 8 weeks were infected with blood-stage P. chabaudi. Malaria parasitemias were significantly higher in these mice than in mice infected with P. chabaudi only. In doubly infected mice, both spleen cell proliferative and Th2 responses to S. mansoni soluble egg antigen (SEA) or anti-CD3 were suppressed up to 1 month after the malaria infection. Findings for SEA-specific immunoglobulin M (IgM) and IgG serum antibody levels were similar. No significant effects were seen on P. chabaudi-induced gamma interferon responses. However, tumor necrosis factor alpha (TNF-α) production was significantly lower in double-infected mice. Thus, a defect in TNF-α production might contribute to the increased malaria parasitemias seen in S. mansoni-P. chabaudi-infected mice. Taken together, our data show that schistosoma and malaria infections profoundly affect each other, findings which might have implications for the development of vaccines.     

Immune Responses to Candida albicans in Genetically Distinct Mice

Mice from six genetically distinct strains were examined for their immune responses to Candida albicans in in vitro and in vivo assays, and naive mice and mice immunized with the fungus were challenged intravenously with three different doses of C. albicans to determine differences in susceptibility. Naive mice from the six groups showed substantial differences in resistance to challenge based on mortalities and quantitative cultures of kidneys, with mice from strains C57BL/6J and BALB/cByJ showing the most resistance; mice from strains A/J, C3H/HeJ, and CBA/J showing moderate susceptibility; and mice from strain DBA/2J showing the highest degree of susceptibility to challenge. Unimmunized mice from strains C57BL/6J and BALB/cByJ did not produce detectable levels of Candida-specific antibody by the end of the 28-day observation period when challenged intravenously, but the other strains did. Immunized mice showed a degree of protection to challenge, with all groups except mice from strain BALB/cByJ showing a reduction of two to three log units in the level of colonization in their kidneys and all strains producing significant levels of antibody. Additionally, the immunized mice of all strains developed substantial levels of delayed-type hypersensitivity and demonstrated nearly identical lymphocyte proliferative responses to Candida antigens. The results indicate that resistance to systemic candidiasis is dependent upon a combination of innate factors, predominately an intact complement system, and the acquisition of an immune response, most likely of a cell-mediated type. Additionally, the findings suggest that genetic control of acquired resistance to C. albicans may not be associated with the H-2 complex.     

Effect of Abrin on Cell-Mediated Immune Responses in Mice

Effect of abrin isolated from Abrus precatorius on the cellular immune responses was studied in normal as well as tumor-bearing animals. Administration of abrin was found to enhance the proliferation of splenocytes and thymocytes (lymphocytes in general) in responses to mitogens. Natural killer cell activity was enhanced significantly by abrin in both the normal (49.8% cell lysis on day 9) and the tumor-bearing group (51.7% cell lysis on day 9), and it was found to be earlier than the control. Antibody dependent cellular cytotoxicity was enhanced in the abrin treated tumor-bearing group on the ninth day (44% cell lysis). An early antibody dependent complement mediated cytotoxicity was observed in the abrin treated group on day 15 (27.6% cell lysis). Results of our present study suggest the immunomodulatory property of abrin.     

Protection Against Meningococcal Challenge Afforded Mice After Immunization with Typhoid-Paratyphoid Vaccine USP

Mice immunized with typhoid-paratyphoid vaccine USP were found to be protected when challenged with serological groups A, B, and C of Neisseria meningitidis. Mice immunized with this vaccine both 14 and 7 days prior to challenge were protected against mean lethal doses (LD₅₀) of 5,220 and 1,151 of groups A and B, respectively, and in two separate experiments they were protected against 3,568 and 268 LD₅₀ of group C. Mice immunized four or more times on successive days prior to challenge were also protected. They demonstrated tolerance and survived a much larger LD₅₀ challenge than mice immunized by any other immunization schedule. Mice immunized once or twice anytime within 7 days prior to challenge were not protected and thus failed to exhibit nonspecific resistance. Serum antibody probably was responsible for the protection afforded mice immunized 14 and 7 days prior to challenge. However, this was not demonstrated conclusively.     

Immune Responses to Pertussis Antigens in Infants and Toddlers after Immunization with Multicomponent Acellular Pertussis Vaccine

Given the resurgence of pertussis despite high rates of vaccination with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine, a better understanding of vaccine-induced immune responses to Bordetella pertussis is needed. We investigated the antibody, cell-mediated, and cytokine responses to B. pertussis antigens in children who received the primary vaccination series (at 2, 4, and 6 months) and first booster vaccination (at 15 to 18 months) with 5-component acellular pertussis (aP) vaccine. The majority of subjects demonstrated a 4-fold increase in antibody titer to all four pertussis antigens (pertussis toxin [PT], pertactin [PRN], filamentous hemagglutinin [FHA], and fimbriae [FIM]) following the primary series and booster vaccination. Following the primary vaccine series, the majority of subjects (52 to 67%) mounted a positive T cell proliferative response (stimulation index of ≥3) to the PT and PRN antigens, while few subjects (7 to 12%) mounted positive proliferative responses to FHA and FIM. One month after booster vaccination (age 16 to 19 months), our study revealed significant increase in gamma interferon (IFN-γ) production in response to the PT and FIM antigens, a significant increase in IL-2 production with the PT, FHA, and PRN antigens, and a lack of significant interleukin-4 (IL-4) secretion with any of the antigens. While previous reports documented a mixed Th1/Th2 or Th2-skewed response to DTaP vaccine in children, our data suggest that following the first DTaP booster, children aged 16 to 19 months have a cytokine profile consistent with a Th1 response, which is known to be essential for clearance of pertussis infection. To better define aP-induced immune responses following the booster vaccine, further studies are needed to assess cytokine responses pre- and postbooster in DTaP recipients.     

Induction of Systemic and Mucosal Immune Responses Following Immunization with Somatostatin-Avidin Complexes Incorporated Into Iscoms

Synthetic, biotinylated somatostatin-14 (Somatotropin Release-Inhibiting Factor; SRIF) was conjugated to avidin, and the resulting complex incorporated into immune-stimulating complexes (ISCOMS). The ISCOMS were used to study the systemic and mucosal immune responses induced by parenteral and gastrointestinal vaccination. Mice were immunized by intraperitoneal (IP) and intragastric (IG) routes and subsequently by either IP or IG secondary immunizations (groups-IP/IP; IP/IG; IG/IG). Antigen specific IgG and IgA antibody secreting cells (ASC) from the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP's) were studied by an enzyme-linked immunospot assay (ELISPOT). Specific proliferative responses of spleen cells to avidin and to SRIF were measured.

Immunization IP/IP evoked the highest serum IgG levels to avidin and to SRIF as well as the highest numbers of splenic IgG isotype ASC. The greatest IgA response in MLN and PP's was induced by IP/IG immunization. Only marginal mucosal immunity and no splenic cell specific proliferative responses were found by IG/IG immunization.

These results indicate that ISCOMS are an effective delivery system for protein-peptide antigens. The ISCOMS system described elicited systemic and mucosal antibody immune responses, and primed specific proliferative response when administered IP/IG. This offers another approach for the design and delivery of mucosally administered peptide vaccines.