Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral bacteria.

An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 µg mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.

Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors.

Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to human nontumorigenic lung cells. The virus-selective oncolytic effect is apoptosis dependent, and related to higher levels of viral transcription, translation and progeny virus formation. Furthermore, NDV-HUJ oncolytic activity is directed in-cis and not through induction of cytokines, that may act in-trans on neighboring cells. Development of primary lung tumors and of the consequent metastasis in mice inoculated with mouse lung tumor cells 3LL-D122 was decreased following treatment with NDV-HUJ. The preferential killing of the tumor cells is not due to a deficiency in the interferon (IFN) system, as expression of the IFN-beta gene, in the infected cells, is properly induced. Moreover, pretreatment with IFN effectively protected the tumor cells from the virus oncolytic effect. We conclude therefore, that NDV-HUJ should have a significant benefit in the treatment of lung cancer as well as other malignancies.

Cranberry juice constituents affect influenza virus adhesion and infectivity.

Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM's potential for inhibiting influenza virus adhesion to cells, and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes (H1N1)and H3N2) and the B type was inhibited by NDM at concentrations of 125 microg/ml or lower, which is at least 20-fold lower than that usually found in cranberry juice. A dose-response effect of NDM on HA was demonstrated. The infectivity of the A and B types was significantly reduced by preincubation with NDM (250 microg/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.

Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections.

Elderberry has been used in folk medicine for centuries to treat influenza, colds and sinusitis, and has been reported to have antiviral activity against influenza and herpes simplex. We investigated the efficacy and safety of oral elderberry syrup for treating influenza A and B infections. Sixty patients (aged 18-54 years) suffering from influenza-like symptoms for 48 h or less were enrolled in this randomized, double-blind, placebo-controlled study during the influenza season of 1999-2000 in Norway. Patients received 15 ml of elderberry or placebo syrup four times a day for 5 days, and recorded their symptoms using a visual analogue scale. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. Elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza. These findings need to be confirmed in a larger study.

Severe influenza infection in a chronic hepatitis C carrier: failure of protective serum HI antibodies after IM vaccination.

BACKGROUND: Influenza is an important cause of morbidity and mortality in immunocompromised hosts. Recommendations exists for vaccination each year, yet disease can still occur. OBJECTIVES: To describe the course of fulminant influenza infection in a patient with HCV. STUDY DESIGN: Case study in which correlation was made between immunoglobulin response to influenza vaccination to the disease and its unique clinical course caused by influenza virus. RESULTS: Influenza A/Jerusalem 17/98 (H(1)N(1)) was isolated from the throat of a chronic hepatitis C carrier who, presented with shortness of breath, and subsequent massive bilateral pneumonia. The patient was previously immunized IM with inactive influenza vaccine. He developed protective levels of humoral antibodies (1:80 hemagglutination inhibition (HI) antibodies) against the three strains of the vaccine that evidently did not prevent respiratory infection. The development of massive bilateral pneumonia and continued presence of influenza virus in the respiratory tract may have been due to his underlying medical condition and possible lack of mucosal secretory IgA (SIgA) antibodies. CONCLUSION: We have presented a case of prolonged influenza infection post vaccination. This case emphasizes the importance of an improved vaccine that would stimulate a better immunologic response, especially in immunocompromised patients.

A novel liposomal influenza vaccine (INFLUSOME-VAC) containing hemagglutinin-neuraminidase and IL-2 or GM-CSF induces protective anti-neuraminidase antibodies cross-reacting with a wide spectrum of influenza A viral strains.

A liposomal influenza vaccine (INFLUSOME-VAC) was developed with the objective of overcoming the major drawbacks of the currently used influenza vaccines: their relatively low efficacy in certain high-risk groups (the elderly, infants, the immunosuppressed) and the need for annual immunization. INFLUSOME-VAC consists of liposomes containing the viral surface proteins hemagglutinin (HA) and neuraminidase (NA) derived from various influenza strains and IL-2 or GM-CSF, as an adjuvant. Vaccination of mice showed that, whereas conventional vaccines induced a low- and short-term response against HA and very low or no anti-NA response, INFLUSOME-VAC produced high titers of both anti-HA and anti-NA antibodies (Abs) in young and old mice that persisted for at least 6 months. Moreover, the anti-NA Abs efficiently cross-reacted with several N2 viral subtypes spanning 20 years, and such vaccines afforded partial protection against heterosubtypic viral infection.

Serum and mucosal immunologic responses in children following the administration of a new inactivated intranasal anti-influenza vaccine.

Children are at considerable risk for influenza infection and may constitute the main vector for transmitting the virus to adults in the community. At present, the use of available vaccines in children is limited mainly because of a fear of side effects from the injection. Intranasal immunization was assessed as a painless, side effect-free method of facilitating the enrollment of children in vaccination programs. One intranasal dose of a trivalent inactive whole virus vaccine containing 20 microg of the three recommended seasonal viral strains was administered to 28 children recruited over two separate winter periods (1997/1998 and 1998/1999). No adverse effects were recorded. Serum IgG responses were determined by the hemagglutination inhibition (HI) method and nasal IgA responses by enzyme-linked immunosorbent assay (ELISA). In both study period seasons, 77.7%-94.4% of children were found to be immune. There was a 3.7 x and 4.7 x increase in geometric mean titer (GMT) for A/H3N2 strains, 1.9 x and 3.9 x for A/H1N1 strains, and a 3.2 x and 1.7 x for B strains in 1997/1998 and 1998/1999, respectively. The increase in GMT, as well as fourfold increases in titer level, was higher when calculated among the nonimmune children prior to vaccination. Of these, 50%-87.5% became immune following immunization. Local antibody response to the three viral strains was detected in 50%-55% of the immunized children. Also, 83.3%, 73.3%, and 61.1% of the vaccinees exhibited a mucosal and/or serum antibody response to the A/Beijing, A/Sydney, and B/Harbin strains, respectively. This mucosal response may forestall influenza development in its early stages, thereby contributing significantly to the reduction of influenza spread in the community.

Is herpes simplex virus associated with pulp/periapical inflammation?

OBJECTIVES: This study focuses on the detection of herpes simplex virus (HSV) DNA in dental pulp and inflamed periapical tissue. STUDY DESIGN: Dental pulp tissue (vital and necrotic) and periapical tissue samples were collected under strictly sterile conditions and examined for the presence of HSV DNA. Saliva samples were also examined for the presence of the viral DNA. The polymerase chain reaction assay was used to detect viral DNA. Blood samples were collected, and the enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against HSV was carried out. RESULTS: According to the ELISA test, 19 of the 23 blood samples were IgG-positive and IgM-negative to HSV, whereas 4 were IgG-negative and IgM-negative. HSV DNA was not detected in the tissue and the saliva samples tested. CONCLUSION: HSV is not present and therefore is probably not involved in the pathology of tooth neural tissue.

Immunoadjuvant activity of interferon-gamma-liposomes co-administered with influenza vaccines.

In an attempt to potentiate the relatively low immunogenicity of the currently used influenza vaccines, especially in high-risk groups, monovalent and divalent subunit vaccine preparations were co-administered with free or liposome-associated murine interferon gamma (mIFNgamma) as an adjuvant. Recombinant murine IFNgamma was entrapped (50-70% efficiency) in two types of large multilamellar vesicles: mIFNgamma-LIP A-'conventional' liposomes, and mIFNgamma-LIP B- 'surface-depleted' liposomes, in which 60 and 8% of the associated cytokine was located at the external liposome membrane, respectively. Subunit preparations containing the viral surface proteins hemagglutinin and neuraminidase (HN) were injected once, i.p. (0.5 microg each), into BALB/c mice, alone and combined with free or liposomal mIFNgamma (mIFNgamma-LIP, 0.5 or 3.0 microg). Sera were tested 3-16 weeks post-vaccination by hemagglutination inhibition (HI), and by ELISA for IgG1 and IgG2a antibodies (Abs). In addition, protective immunity against intranasal viral infection was assayed at 11 and 17 weeks post-vaccination. The results showed that: (a) Vaccination with HN alone produces very low HI and IgG titers and does not afford any protection. (b) Although co-administration with free mIFNgamma (particularly using 3.0 microg) markedly enhances HI titer as well as the IgG1 and IgG2a levels, protection is negligible (0-33%). (c) In most cases, mIFNgamma-LIP is significantly more potent than free mIFNgamma (2-40-fold increase in Ab titer), and the low dose (0.5 microg) is generally more efficient than the high dose. Up to 83% of the mice co-vaccinated with mIFNgamma-LIP were protected against viral challenge. (d) Both the IgG2a level and the HI titer appear to be crucial for protection. (e) Although the two liposomal preparations differ in their cytokine release profile in vivo and in their bioactivity in vitro, their adjuvant activity is comparable.

A double-blind trial of a new inactivated, trivalent, intra-nasal anti-influenza vaccine in general practice: relationship between immunogenicity and respiratory morbidity over the winter of 1997-98.

BACKGROUND: Influenza is responsible for considerable morbidity not only among older people but in younger age groups as well. However, most large-scale anti-influenza vaccination campaigns are still aimed principally at the elderly using injectable vaccines. Until now there has been much less emphasis on targeting younger populations or using intra-nasal vaccines in mass anti-influenza immunisation programmes. OBJECTIVES: To assess the immunogenicity of a new inactivated intra-nasal anti-influenza vaccine and to measure its effect on respiratory morbidity in a volunteer general practice population. STUDY DESIGN: A prospective, double-blind, placebo-controlled trial using the new vaccine was carried out over the winter of 1997-98 on 274 healthy patients aged 12-60 from three Israeli general practices, 182 in the vaccine group and 92 in the placebo group. Following vaccination the changes in the antigen levels and episodes of respiratory illness in the vaccine and placebo groups were measured. RESULTS: Protective antibody levels occurred after a single dose of vaccine [influenza H1N1, 41% immune pre-vaccination to 73% post-vaccination; influenza H3N2, 35-66%; influenza B, 27-64%]. Between January and March 1998, when influenza activity was at a peak in Israel, the average number of respiratory illness events in the vaccine group [14 events/100 subjects per month] was significantly less than in the placebo group [22 events/100 subjects per month]; similarly, the average number of respiratory illness days in the vaccine group over the same period [69 days/100 subjects per month] was significantly less than in the placebo group [117 days/100 subjects per month]. CONCLUSIONS: The new vaccine possessed significant immunogenicity and was associated with a significant reduction in respiratory morbidity among a group of healthy older children and adults. Since intra-nasal vaccines are simpler to administer and more acceptable to the public than injections the vaccine's potential for use in routine anti-influenza vaccination campaigns seems promising, especially if its beneficial effects are also reproducible in more medically vulnerable populations.

Local and systemic immune response in community-dwelling elderly after intranasal or intramuscular immunization with inactivated influenza vaccine.

Intramuscular (IM) influenza vaccines are about 50% effective in preventing clinical illness among the elderly and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among community-dwelling elderly. Sixty-one subjects were vaccinated with two doses of an IN vaccine and a control group of 31 subjects was vaccinated with a commercial IM vaccine. Viral strains in the 1997/8 vaccine used were A/Nanchang/933/95(H3N2), A/Johannesburg/82/96(H1N1) and B/Harbin/7/94. Serum IgG and nasal IgA were determined by HI and ELISA, respectively. Only a few minor local adverse events were reported after vaccination. Seroconversion for the three antigens tested was higher after IM vaccination, although not statistically significant. Local antibody response to the three antigens tested was detected in 50-53% and 19-26% of IN and IM immunized subjects, respectively. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of complications in the elderly.

Local SIgA response following administration of a novel intranasal inactivated influenza virus vaccine in community residing elderly.

Community-residing elderly were immunized twice intranasally three weeks apart with a new inactivated whole influenza vaccine. A control group was immunized intramuscularly with conventional influenza vaccine. Local antibody response was detected in about 50% of intranasally immunized subjects compared to about 20% of intramuscularly immunized subjects, to the three viral strains. Increasing the incidence of elevated IgA response may prevent influenza at its early stages thus reducing complications in the elderly.

A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. I. Vaccine characterization and efficacy studies in mice.

The aim of this study was to improve the potency of the currently used influenza subunit vaccines, which are of relatively low efficiency in high-risk groups. Influenza A virus (Shangdong/9/93) haemagglutinin/neuraminidase (H3N2), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were encapsulated, each separately or combined, in multilamellar vesicles composed of dimyristoyl phosphatidylcholine. BALB/c mice were immunized once, i.p. or s.c., with 0.05-2.0 microg HN administered either as free antigen (F-HN), adsorbed to aluminum hydroxide (Al-HN), or encapsulated in liposomes (Lip-HN), separately or together with 1 x 10(2)-4.5 x 10(4) units of free or encapsulated cytokines. Serum antibodies were assayed on days 11-360 by the haemagglutination-inhibition (HI) test and ELISA. Protective immunity against intranasal virus challenge was determined at 9-14 months post-vaccination. The following results were obtained: (1) The efficiency of encapsulation in liposomes was 95, 90 and 38% for HN, IL-2 and GM-CSF, respectively, and the liposomal preparations were highly stable as an aqueous dispersion for > 2 months at 4 degrees C. (2) Following immunization with 0.5 microg Lip-HN, there was an earlier, up to 50-fold stronger, and 3-5 times longer response than that obtained with nonliposomal HN. (3) Coimmunization with free cytokines further increased the response 2-20 times and the two cytokines had an additive effect. (4) Liposomal cytokines were 2-20 times more effective than the free cytokines and their stimulatory effect was more durable. (5) A 100% seroconversion (HI titer > or = 40) was achieved with only 10-25% of the routinely used antigen dose, by encapsulating either antigen or cytokine. (6) The level of protection following vaccination with the combined liposomal vaccines was 70-100% versus 0-25% in mice immunized with Al-HN alone, and no toxicity was observed. In conclusion, our animal experiments show that the liposomal vaccines are superior to the currently used influenza vaccines, increasing the response by 2-3 orders of magnitude in mice. This approach may also prove valuable for subunit vaccines against other microorganisms.

A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. II. Induction of TH1 and TH2 responses in mice.

This study was aimed at analyzing, in parallel, the humoral and cellular immune responses elicited in mice immunized with liposomal influenza A (Shangdong/9/93) subunit vaccines composed of haemagglutinin/neuraminidase (H3N2) and IL-2 or GM-CSF. Recently, we reported that such vaccines evoke a more rapid, stronger and longer-lasting (over 1 year) humoral response, as well as protective immunity against viral infection, following a single administration, as compared with the response induced by the free antigen given alone or together with soluble cytokines. In the present study, BALB/C mice were immunized once, i.p., s.c., i.m. or i.n., with nonliposomal or liposomal vaccines and the humoral (antibody titer and isotypes) and cellular (DTH, cytotoxicity, cytokine production) responses were assessed at various times (2-56 weeks). The main findings were: (a) the combined liposomal vaccines consisting of encapsulated antigen and encapsulated cytokine, but not the free antigen, elicited a high titer of serum IgG1, IgG2a, IgG3 and IgM antibodies; (b) the combined liposomal vaccines were efficient following administration by the various routes, and induced a local (in lung) IgA response in i.n. vaccinated mice; (c) the liposomal vaccines triggered DTH and cytotoxic responses, as well as cytokine (mainly IL-4) production. Together, these and other findings indicate that our cytokine-supported liposomal influenza vaccines efficiently stimulate both Th1 and Th2 responses and that such vaccines may be more potent in high-risk groups than the currently used subunit vaccines.

Tumorigenicity and immunogenicity in a murine model of B-cell leukemia/lymphoma (BCL1).

Multiple injections of intact irradiated BCL1 cells, a murine B-cell leukemia/lymphoma can trigger a dose-dependent anti-tumor immune response in naive syngeneic mice. The ability to induce anti-BCL1 immunity and the effect of various cell-modifications on BCL1 tumorigenicity and immunogenicity was evaluated. Newcastle disease virus (NDV) infection or transfer of cytokine genes by both retroviral and Adeno 5 vectors affect neither tumorigenicity nor immunogenicity of BCL1 cells given as a non-immunogenic cell-dose. New ways will have to be developed to elicit a reliable and reproducible anti-tumor effect in spontaneously arising and non-immunogenic hematological malignancies.

The influence of sequential annual vaccination and of DHEA administration on the efficacy of the immune response to influenza vaccine in the elderly.

The present study examined the effect of repeated vaccination and of dehydroepiandrosterone (DHEA) treatment on the immune response to influenza vaccine in elderly subjects. Seventy-one elderly volunteers, aged 61-89 years, enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. for 4 consecutive days starting 2 days before immunization) or placebo. Antibody response against the three strains of vaccine was measured before and 28 days after vaccination, and compared between previously vaccinated and non-vaccinated subjects. DHEA treatment did not enhance established immunity. A significant decrease in attainment of protective antibody titer (titer of 1:40 or greater) against A/Texas in subjects with non-protective baseline antibody titer was recorded following DHEA treatment compared to placebo (52 vs. 84%, P < 0.05). Post-immunization titers against influenza A strains were significantly higher in those subjects who were never immunized before. Additionally, post-vaccination protective titers against the A/Johannesburg strain were more prevalent in those subjects who were never vaccinated before. The results were not the same for anti-B/Harbin antibodies-repeated vaccination caused a non-significant increase in HI titer in previously vaccinated subjects.

Host factors affecting the homologous and heterologous immune response of cattle to FMDV: genetic background, age, virus strains and route of administration.

Sixty bulls were tested for antibodies to the heterologous serotype C1 of FMDV following repeatable vaccinations with a commercial trivalent vaccine (O1, A22, Asia1). Six (10%) bulls were found to possess rather high levels of heterologous neutralizing antibodies which showed accumulative trend with age. Two high positive and two negative bulls for the heterologous serotype C1 were selected for progeny test involving ten daughters of each bull. The four bulls, either positive or negative for the heterologous serotype C1, showed significant phenotypic correlation between their heterologous and homologous titers (O1, A22, Asia1). This correlation between heterologous and homologous antibody titers was not found in the daughters of these bulls. However, two of ten daughters of one positive bull, to C1 showed individual high titers (> or = 1.5). The intradermal (ID) as compared to subcutaneous (SC) route of administration resulted in higher rate of responders to both heterologous serotypes C1 and SAT1. The heterologous immune response to FMDV in Israeli-Friesian cattle was found to be related to the age of the host, multiplicity of vaccinations, route of vaccination, kind and numbers of the antigens used in the vaccine. The homologous immune response is also controlled by genetic factors.

Antibodies to cytomegalo and Epstein-Barr viruses in human saliva and gingival fluid.

The prevalence of antibodies to EBV and CMV was studied in 34 samples of whole saliva and gingival crevicular fluids (GCF) obtained from clinically healthy volunteers and compared to the corresponding antibodies present in the serum of each individual. Higher prevalence of serum antibodies was found to EBV (85.2%) than to CMV (64.7%) (P < 0.04). The percentage of saliva samples containing IgG and/or IgA antibodies was not significantly different for the two viruses (79.4% for EBV and 58.8% for CMV). However, in the GCF the percentage to EBV was lower-32.3% as compared to 70.5% for CMV (P < 0.002). The prevalence of CMV in serum saliva and GCF was similar. However, while in the saliva similar levels of IgG and IgA were found, in the GCF IgA prevails. The picture for EBV is different: a similar percentage of antibodies was noticed in serum and saliva, but it was significantly lower in the GCF. However, antibodies to EBV were mostly IgA both in the saliva and the GCF. Although a similar number of samples were positive to both viruses in the saliva, the IgA response to EBV was higher than to CMV (P < 0.05), while in GCF IgA response was higher to CMV (P < 0.05). Passive transudation rather than active transport of plasma-derived Ig is probably responsible for the presence of IgG, while the IgA found in saliva and GCF is derived from local synthesis by plasma cells rather than from selective transport from blood.

Isolation of influenza C virus during an outbreak of influenza A and B viruses.

During the winter of 1996 to 1997 two cases of influenza C were confirmed, one by isolation and the second by serology (fourfold increase in hemagglutination inhibition antibodies). The cases of influenza C occurred during an outbreak of influenza A (H3N2) and B viruses. The positive isolation was from one of three throat washings sent to the laboratory, and the other case was from a group of 51 students participating in a study of influenza virus vaccination. It seems, therefore, that influenza C virus should also be considered when examining patients with respiratory infections during the influenza season.

Homologous and heterologous antibody response of cattle and sheep after vaccination with foot and mouth disease and influenza viruses.

Homologous and heterologous antibody response to FMD and influenza vaccines was studied in 37 calves and 45 lambs at the age of 2 months. The FMD and influenza monovalent killed vaccines were administered simultaneously twice. Another group of 18 calves was vaccinated twice, first at the age of 2 months and second at the age of 6 months, with trivalent FMD vaccine. The antibody titers were measured by ELISA and HI after second vaccination, for FMDV and influenza, respectively. The conclusions of this study are summarized as follows. Individuals, lambs and calves, that cross-respond to one heterologous serotype are liable to respond to another heterologous serotype of the same virus. Individuals, lambs and calves, showing double cross-reactivity to one virus (FMDV), are highly liable to show double cross-reactivity to entirely another virus (Influenza). Multivalent vaccines of FMDV are expected to elevate the antibody titers for at least one heterologous serotype (not included in the vaccine) and to detect antibodies for an additional heterologous serotype, not detected otherwise following monovalent vaccination. These results indicate the important role of the host in the spectrum of the specific immune response.