Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria

Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.     

Spontaneous intracranial hypotension: spinal MR findings

Several melanosome glycoproteins have been shown to be antigenic in humans. Correlation of antigen-specific immune responses in patients with the autoimmune disease vitiligo, therapy-induced hypopigmentation, and cutaneous melanoma has not been well studied. We examined antibody responses to a melanocyte autoantigen, tyrosinase-related protein-2 (TRP-2), as it is highly expressed in cutaneous melanoma and melanocytes. TRP-2 recombinant protein was synthesized for western blot and affinity anti-TRP-2 enzyme-linked immunosorbent assay. We demonstrated that patients with malignant melanoma, vitiligo, and active-specific immunotherapy-induced depigmentation had significant anti-TRP-2 IgG titers. The highest level of anti-TRP-2 IgG response was found in vitiligo patients. Induction and enhancement of anti-TRP-2 IgG responses were observed in melanoma patients treated with a polyvalent melanoma cell vaccine containing TRP-2. Active-specific immunotherapy could induce and/or augment the TRP-2 IgG antibody titers. Melanoma patients who developed hypopigmentation and had improved survival after polyvalent melanoma cell vaccine had significantly augmented anti-TRP-2 antibody responses compared with patients with poor prognosis. This study demonstrates that TRP-2 autoantigen is immunogenic in humans. TRP-2 antibody responses provide a linkage between autoimmune responses by vitiligo patients and melanoma patients responding to immunotherapy who have induced hypopigmentation.     

Oral immunization with recombinant vaccina expressing cell-surface-anchored beta hCG induces anti-hCG antibodies and T-cell proliferative response in rats

A vaccinia recombinant, VSS2, expressing cell-surface-anchored beta-subunit of human chorionic gonadotropin (beta hCG) has earlier been found to induce high titered anti-hCG antibodies in rats immunized by tail scarification. The immunogenicity of this recombinant was compared in rats which received the virus through different routes of inoculation: intradermal, intragastric, intrajejunal or by tail scarification. The recombinant virus induced high titers of anti-hCG antibodies in all instances although the titers were about one log lower when the recombinant virus was delivered orally. The recombinant was found to induce T-cell proliferative response in rats of all immunization groups.     

Histamine levels in the blood of humans experimental animals under normal conditions and following vaccination]

The authors present the results of study of the blood histamine content in intact rabbits and in the animals to which commercial vaccines with a different degree of reactogenic property for man were administered. The blood histamine level was also studied in practically healthy individuals and in those vaccinated with inactivated tick-borne encephalitis vaccine. The blood histamine content varied in intact rabbits from 4 to 10 microgram/ml, averaging 6.4 +/- 0.09 microgram/ml. Animal immunization caused elevation of the blood histamine content correlating with the reactogenic properties of the preparations for man: vaccines with low reactogenic properties--inactivated encephalitis and live measles vaccine produced no significant changes in the index under study; as to the typhoid vaccine with sextatoxoid, and smallpox vaccine with marked reactogenic properties--they stimulated significant histaminemia in rabbits. Revaccination of man against tick-borne encephalitis with the inactivated cultural vaccine caused an increase in the blood histamine content.     

Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses

Recombinant vaccinia viruses containing tumor associated genes represent an attractive vector to induce immune responses to weak immunogens in cancer immunotherapy protocols. The property of intense immunogenicity of vaccinia proteins, however, also serves to limit the number of inoculations of recombinant vaccinia viruses. Host immune responses to the first immunization have been shown to limit the replication of subsequent vaccinations and thus reduce effectiveness of boost inoculations. The use of recombinant avian pox viruses (avipox) such as the canarypox (ALVAC) or fowlpox are potential candidates for immunization protocols in that they can infect mammalian cells and express the inserted transgene, but do not replicate in mammalian cells. We report here the construction and characterization of a canarypox (ALVAC) recombinant expressing the human carcinoembryonic antigen (CEA) gene (designated ALVAC-CEA). Antibody, lymphoproliferative and cytolytic T-cell responses as well as tumor inhibition were shown to be elicited by the ALVAC-CEA recombinant in a murine model. The utilization of a diversified immunization scheme using a recombinant vaccinia virus followed by recombinant avian pox virus was shown to be far superior than the use of either one alone in eliciting CEA-specific T-cell responses. Experiments were conducted to determine if the use of a diversified immunization scheme using a recombinant vaccinia virus (rV-CEA) and ALVAC-CEA would be superior to the use of either one alone in eliciting CEA-specific T-cell responses. When mice were immunized with rV-CEA and then ALVAC-CEA. CEA-specific T-cell responses were at least four times greater, and for superior to those achieved with three immunizations of ALVAC-CEA. Multiple boosts of ALVAC-CEA following rV-CEA immunization further potentiated anti-tumor effects and CEA specific T-cell responses. These studies demonstrate the proof of concept of the advantage of diversified immunization protocols employing both recombinant vaccinia and recombinant avipox vectors.     

Field trial of a vaccine against New World cutaneous leishmaniasis in an at-risk child population: safety, immunogenicity, and efficacy during the first 12 months of follow-up

The safety, immunogenicity, and efficacy of a vaccine against cutaneous leishmaniasis in rural Ecuadorian children was assessed in a randomized, controlled, double-blinded study. Vaccine group subjects received 2 intradermal doses of a whole, killed promastigote vaccine cocktail plus bacille Calmette-Guérin (BCG) adjuvant. Control subjects got 2 doses of BCG only. The subjects who received both vaccination doses, 438 in the vaccine group (79.3%) and 406 in the control group (83.4%), were followed for 12 months. No serious adverse side effects were identified in either group. Significantly more vaccine group subjects than controls converted to a positive Montenegro skin test (85.1% vs. 20.1%; chi2 = 279; P < .001). The incidence of cutaneous leishmaniasis was significantly reduced in the vaccine compared with the control group (2.1% vs. 7.6%; chi2 = 8.95; P < .003). The protective efficacy of the vaccine was 72.9% (95% confidence interval = 36.1%-88.5%).     

Progressive vaccinia treated with ribavirin and vaccinia immune globulin

A 67-year-old man with metastatic melanoma and chronic lymphocytic leukemia was inadvertently given a vaccinia melanoma oncolysate vaccination. He developed progressive vaccinia at the site of inoculation. The lesion started to heal only when he was treated with ribavirin. Vaccinia immune globulin was administered and appeared to help control the initial lesion and limit the development of satellite lesions.     

Immunization of healthy adult subjects in the United States with inactivated Mycobacterium vaccae administered in a three-dose series

Heat-killed Mycobacterium vaccae vaccine was administered in a three-dose intradermal schedule to 10 healthy adult volunteers at 0, 2, and 10 months. Local and systemic side effects were monitored and vaccine site reactions were measured and photographed at visits 2 days, 14 days, and 2 months after each dose. Reactions to skin tests with purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS) and titers of antibody to arabinose lipoarabinomannin were determined at baseline and after each dose of vaccine. Lymphocyte proliferation responses to MAS were determined after the final dose of vaccine. Immunization was safe and well tolerated, with maximal induration (range, 6-25 mm) at 2 days. PPD skin test conversions did not occur. Seven subjects completed the three-dose schedule; preexisting immunologic responses to mycobacteria were boosted in three, and a new response was elicited in one. M. vaccae vaccine is safe and induces measurable immunologic responses to mycobacterial antigens in some healthy adults.     

Cross-clade cytotoxic T cell response to human immunodeficiency virus type 1 proteins among HLA disparate North Americans and Thais

A globally effective vaccine will need to elicit cytotoxic T lymphocytes (CTL) capable of recognizing diverse human immunodeficiency virus type 1 (HIV-1) clades. Study of the cellular immune responses of HIV-1-infected persons may allow predictions to be made regarding useful vaccine antigen components. The frequency and magnitude of CTL responses to clade E and B Gag, Pol-RT, Env, and Nef proteins were compared in 12 HLA-characterized, clade E-infected Thais and in 10 clade B-infected North Americans using vaccinia recombinant constructs for protein expression. While responses were detected against all proteins, they were most frequent and cross-reactive to Gag in both groups. Pol-RT was recognized less frequently in Thais than North Americans. Cross-clade protein recognition was common but not uniformly present among these HLA-disparate individuals. Population-specific CTL data are needed to adequately prepare for vaccine trials outside of North America and Europe.     

Lymphocyte and macrophage responses after vaccinia virus infections

Using a semimicromethod with washed whole blood, in vitro lymphocyte responses of rabbits to intradermal infection with vaccinia virus was studied. Peritoneal exudate macrophages were infected with vaccinia in vitro to determine the time of appearance of activated macrophages. After primary infection, an increase in spontaneous incorporation of thymidine by blood cultures was found as early as 2 days postinfection. This effect was at a maximum at 7 to 10 days, with counts up to 100-fold higher than before infection. Incubation of these cultures with concanavalin A showed a marked decrease in stimulation index as compared with normals. Although only a transient stimulation with vaccinia was found during the acute infection, stimulation indexes of 2 to 3 were obtained during convalescence. Macrophages from rabbits early after infection supported vaccinia replication, whereas those at day 6 or later resisted infection. Macrophage resistance persisted for 2 to 3 weeks. The response of lymphocytes from rabbits reinfected with vaccinia after 15 weeks differed, with a small increase in spontaneous thymidine uptake, a smaller depression in concanavalin A stimulation, and a greater specific response to vaccinia. Macrophage activation occurred earlier and persisted for a longer time after secondary infection.     

Rational approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids

Adverse reactions to routine vaccines are obstacles to the mass vaccination campaigns. Though the absolute safety of any injectable vaccine cannot be guaranteed, the adverse side effects to vaccines can be minimized by practicing existing scientific knowledge. Adverse side effects to tetanus and diphtheria toxoids have been known for many years and there have been ways to minimize these reactions. These procedures did not get wide acceptance, because the current partially purified tetanus and diphtheria vaccines meet the regulatory requirements and the manufacturers are reluctant to change the established procedures of production due to the amount of work involved in the regulatory issues under the current Good Manufacturing Practices (GMP). Due to the recent epidemic of diphtheria in the independent states of the former Soviet Union, and its potential for spread to other European Countries, vaccination campaigns with tetanus and diphtheria vaccines received a new boost with several international agencies. In this report, we review the causes for adverse reactions to tetanus and diphtheria vaccines and offer practical suggestions for minimizing these reactions. The major issues in minimizing adverse reactions to these vaccines include: (1) purifying the toxins before detoxification as the reactogenic accessory antigens get covalently bound to the toxins during detoxification; (2) either using well-tolerated adjuvants which do not elicit the production of antigenic specific IgE antibodies responsible for adverse reactions or by using non-adjuvanted highly immunogenic polymerized antigens; (3) checking the status of immunity by recently developed rapid serological methods or by the Schick skin-test for diphtheria to avoid allergic or Arthus-type reactions. These approaches are applicable to industrial scales and would result in a pure, less reactogenic and better characterized toxoids antigens which would be more suitable for combined vaccines comprising highly purified acellular pertussis components, polysaccharide-protein conjugates and other antigens.     

Role of preimmunization virus sequences in cellular immunity in HIV-infected patients during HIV type 1 MN recombinant gp160 immunization

The effect of patient preimmunization virus sequences on CTL responses during gp160 immunization were studied. Ten HLA-A2+, HIV+ asymptomatic patients with CD4+ T cells >500/mm3 were given two courses of HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific CTL responses, using PBMCs, were measured against peptide-coated autologous B lymphoblastoid cell lines. Optimum CTL epitopes were determined by HLA-A2-binding affinity of 9- to 10-mer peptides containing the HLA-A2.1-binding motif. Ten of the high- or intermediate-binding peptides were conserved among >50% of reported clade B HIV strains. These peptide-specific CTL activities and the patient virus sequences in peptide-coding regions were monitored. Six patients showed envelope peptide-specific CTL responses, which correlated with the presence of whole envelope antigen-specific CTL responses. Five of these patients, who showed responses to epitopes in the gp41 region (aa 814-824), had preimmunization virus similar to the vaccine sequence in this region. Three patients who did not show these epitope-specific responses had initially different sequences in the HIV gene encoding that region. The epitope-specific CTL responses appear to reflect recall responses, as only patients infected with virus containing the vaccine sequence developed them and they could be recalled with a second set of vaccine injections. This appears to be reminiscent of the concept of T cell "original antigenic sin." This vaccine was also immunogenic as measured by gp160-specific lymphocyte-proliferative responses. However, increased immune responses did not impact the HIV load or CTL epitope sequences during therapy.     

Intranasal application of inactivated influenza virus vaccines

Recent concept on the common mucosal immune system gives new direction of influenza vaccine development-mucosal vaccine. Vaccines have to be administered over the mucosal surface (in case of influenza vaccine, intranasal route may be the most suited route) to assure mucosal immunity which is the first hand armament against influenza virus. This article reviews our work on intranasal administration of inactivated influenza virus HA vaccines. Since influenza vaccines are usually given to people who has some degree of immunity due to past infection or immunization, vaccines which have booster effect are preferable. In this context, intranasally administered inactivated influenza HA vaccine was more immunogenic than cold adapted reassortant live influenza virus vaccine, another candidate mucosal influenza virus vaccine, which is now under investigation in the United States.     

Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents

BACKGROUND: The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents. Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old, the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group. MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days postvaccination using diary cards. Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components. RESULTS: Both vaccines showed good tolerability, local and general reactogenicity being similar. For local reactions Group 1=88.1% and Group 2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV. The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune responses were obtained against all vaccine components. CONCLUSIONS: The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents. To prevent recent resurgence of pertussis in France, this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France.     

Humoral and cellular immune responses of dogs immunized with a nucleic acid vaccine encoding human carcinoembryonic antigen

A nucleic acid vaccine encoding human carcinoembryonic antigen (CEA) was administered to 10 juvenile dogs, 10-15 weeks of age, by four parenteral routes. The routes tested were intramuscular injection using a needle and syringe, intramuscular injection using the Biojector needleless injection device, intradermal injection or intravenous injection. All groups received 150 micrograms of plasmid DNA on weeks 0, 4, 7 and 13. All dogs were bled weekly for 17 weeks and tested for antibody against human CEA. Dogs given plasmid intramuscularly either by needle and syringe or Biojector showed significant antibody responses by week 9 which peaked by week 15. Dogs receiving plasmid intravenously showed slight, unsustained increases in antibody titers while dogs receiving plasmid intradermally had significant titers, but at levels approximately one log less than those induced by intramuscular injection. The five dogs immunized by intramuscular delivery of plasmid DNA were examined for cellular immune responses to human CEA by lymphoblast transformation (LBT) assay. All five showed significant CEA-specific lymphoproliferation when compared with unvaccinated dogs. Physical examination, clinical chemistry, hematology and histopathology examinations revealed no abnormalities associated with nucleic acid immunization.     

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.     

Lispro analog for treatment of generalized allergy to human insulin

OBJECTIVE: To evaluate the clinical usefulness of the human insulin analog lispro in a patient with generalized allergy to human insulin. RESEARCH DESIGN AND METHODS: A 34-year-old obese female patient developed systemic allergic reactions to human insulin but tolerated insulin lispro. Sequential analyses of the anti-insulin IgE and IgG immunoglobulins were performed. RESULTS: On intradermal test, the lispro insulin produced a 50% less intense wheal-flare response, compared with human insulin, which was presumed to be due to lispro's molecular form. The intradermal reactivity to both human and lispro insulins decreased with time and disappeared by week 25. 125I-labeled lispro and human insulin binding antibody titers of both the IgE and IgG immunoglobulins were high initially, but decreased progressively, becoming very low by the end of 1 year. In in vitro immunoassay, the lispro and human insulins show a complete cross-reactivity. CONCLUSIONS: Lispro may be useful for the management of allergy to human insulin. This analog of human insulin appears to have a reduced immunogenic potency.     

A clinicopathological study of the effects of topical retinyl propionate cream in skin photoageing

To study the influence exerted by cutaneous ligands in nickel reactions we have evaluated the patch tests responses to 4 aqueous nickel salts (sulfate, chloride, nitrate, acetate) able to form different complexes with different geometry. Two groups of respectively 71 subjects who previously reacted only to nickel sulfate 5% petrolatum (pet) and of 30 subjects who previously reacted to nickel sulfate 5% pet and to at least 1 other transition metal, were simultaneously repatch-tested to 200 microg of Ni++ contained in nickel sulfate in pet and to 47 microg of Ni++ contained in 4 different aqueous nickel salts. Another 2 groups of 25 subjects with the same characteristics were simultaneously repatch tested to 200 microg of Ni++ in pet and to 12 microg of aq Ni++ as in the first 2 groups. Visual score, total score, and mean value of the reactions were utilized in evaluating the degree of the responses. On testing to 200 microg of Ni++ in pet all the subjects were able to give positive responses. Whilst a higher percentage of the responses of 2+ degrees was found in subjects reacting to nickel sulfate 5% pet alone, a higher percentage of responses of 3+ degrees was observed in subjects reacting to more transition metals. On testing to 47 and 12 microg of aqueous Ni++ a large variability of responses to the single salts was observed in all the subjects. However, in subjects reacting to more metals there were either a greater number of multiple responses to 3 or 4 salts or responses stronger than those found in subjects reacting to nickel sulfate alone. Although patch testing cannot give us complete information about the degree of previous exposure, the results arising from the tests seem to demonstrate that the subjects allergic to nickel and other transition metals are more reactive than the subjects allergic only to nickel to the application of the same amounts of Ni++ contained in different salts. When considering the QSAR model, the difference in the sensitizing potential of the metal at the same penetration properties can depend on the possibility of combining with specific ligands. Therefore, it is likely that in subjects reacting to more metals there is a more uniform availability of cutaneous ligands which conditions the formation of complexes more immunogenic. The arising inflammatory reaction in these cases leads to a stronger but less specific response.     

Leishmania mexicana in C3H mice: BCG and levamisole treatment of established infections

The effect of BCG and levamisole on the course of established murine leishmaniasis was examined. C3H mice infected subcutaneously in the perinasal region with 10(5) L. mexicana promastigotes produced chronic non-ulcerating, non-healing lesions and demonstrated positive humoral and delayed hypersensitivity responses to leishmanial antigens. Infected animals were treated during months 3-5 of infection with either live BCG or with levamisole. Neither treatment resulted in resolution of lesions or in production of a hyperallergic form of infection; similarly, neither immune responses to leishmanial antigens nor histopathological features of lesions were significantly altered. BCG treatment resulted in accelerated growth of primary leishmanial lesions and in the appearance of metastases in some animals. Levamisole treatment of uninfected animals resulted in low levels of antibodies reacting with promastigote antigens, but not in positive delayed intradermal responses. BCG induced delayed intradermal sensitivity to PPD in both infected and control animals; significantly increased delayed reactions to leishmania, were observed in treated uninfected mice.     

Characterization of cytokine production in murine Trypanosoma cruzi infection by in situ immunocytochemistry: lack of association between susceptibility and type 2 cytokine production

The ability of subcutaneous pretreatment with an immunogenic peptide derived from Fel d I, the major cat protein, to suppress the development of allergic responses was examined in a mouse model of antigen-induced sensitization. BALB/c mice exposed to aerosolized Fel d I chain 1 peptide developed antigen-specific IgE responses, immediate cutaneous reactivity to the peptide, and increased airway responsiveness (AR). Both subcutaneous and intraperitoneal administration of the peptide prior to sensitization caused a 50% reduction in cutaneous reactivity which was associated with a decrease in serum anti-Fel d I chain 1 IgE and IgG1 antibody responses and an increase in specific IgG. Pretreatment with the peptide also suppressed spleen and lymph node proliferative responses to the peptide. However, only subcutaneous peptide injections could prevent the development of increased AR. Transfer of spleen cells from subcutaneously peptide-treated mice to sensitized recipients reduced serum antigen-specific IgE and IgG1 antibody responses and skin test reactivity, and prevented alterations in AR. These data suggest that IgE (and IgG1) responses and airway hyperresponsiveness induced by allergen sensitization via the airways can be modulated by subcutaneous administration of peptide. Further, the results define a model for investigating the modulatory effects of subcutaneous administration of immunogenic peptides or protein on an ongoing allergic response.