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Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen.

The purpose of this study was to determine whether a combination of two anti-idiotypic antibodies that mimic the high molecular weight proteoglycan antigen found on most melanoma tumors was capable of enhancing cellular immunity in vaccinated high-risk patients with melanoma. Twenty-eight stage I-IV high-risk patients with melanoma were immunized with a mixture of variable concentrations of MELIMMUNE-1 and MELIMMUNE-2, along with the adjuvant SAF-m, using two immunization schedules. Peripheral blood mononuclear cells were collected before the first immunization and 4 weeks after the final immunization and tested for in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 and for cytotoxicity against 51Cr-labeled target cell lines. Additionally, supernatants from in vitro proliferation cultures were tested for interleukin 10 and IFN-gamma levels. Significant in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 were observed in postimmunization samples but not in prevaccination samples. The mean stimulation index for MELIMMUNE-2 (33.7 +/- 0.6) was significantly higher than that for MELIMMUNE-1 (13.9 +/- 0.3; P < 0.025). Supernatants obtained from 78% of the in vitro stimulated cultures pre- or postvaccination contained significant levels of interleukin 10 (range, 0.43-142 pg/ml), whereas IFN-gamma levels were elevated in 53% of postvaccination samples (range, 3-245 pg/ml) but not prevaccination samples. More importantly, we were able to generate specific CTL responses in 43% of the patients, which correlated with elevated IFN-gamma levels. These results indicate that MELIMMUNE enhances cell-mediated immunity in patients with melanoma.

Antibodies, Anti-Idiotypic↗

Rationale for the sequential use of inactivated poliovirus vaccine and live attenuated poliovirus vaccine for routine poliomyelitis immunization in the United States.

Despite the concerns mentioned in the last section, there are many reasons to believe that a polio immunization schedule that incorporates sequential doses of inactivated poliovirus vaccine and live attenuated poliovirus vaccine would provide both humoral and intestinal immunity to the fully immunized person that is at least as good, if not better, than the immunity achieved by the use of IPV or OPV alone. A substantial degree of protection should also extend to partially immunized and unimmunized preschool aged children in the community. Furthermore most of the cases of OPV-associated paralytic poliomyelitis could be prevented. Because the reasons for these beliefs are based on data from small studies and on inferences from related research, specific recommendations for a change from current polio immunization policy must depend on additional clinical research. Well-designed trials comparing several different options for sequencing both inactivated and live vaccines are needed, and these studies should focus carefully on both humoral and intestinal immunity conferred by the various vaccine schedules.

Drug Administration Schedule↗

Antibody response of children to measles vaccine mixed with diphtheria-pertussis-tetanus or diphtheria-pertussis-tetanus-poliomyelitis vaccine.

The feasibility of giving measles vaccine mixed with either diphtheria-pertussis-tetanus (DPT) or DPT-poliomyelitis (DPTP) vaccine was investigated to simplify the routine immunization schedule. Children 12 to 18 months of age, due for measles immunization, were given measles vaccine alone or mixed with DPT or DPTP. Their prevaccination and four-weeks postvaccination serum samples were tested for the measles virus hemagglutination-inhibition antibody titer. Although 191 children completed the study, only 160 were initially seronegative. The seroconversion rates and geometric mean antibody titers in children given measles vaccine alone, mixed with DPT, or mixed with DPTP were 98%, 96.3%, and 96.4% and 41, 53, and 53, respectively. Local and systemic reactions were no more frequent in children given the mixture of vaccines than in children given DPTP alone. In summary, injecting measles vaccine mixed with DPT or DPTP did not diminish its immunogenic potency or increase adverse reactions. We believe that freshly mixed measles and DPT or DPTP vaccines can be given together, thus avoiding two separate injections.

Antibodies, Viral↗

Impact of therapeutic immunization on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection.

BACKGROUND: Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable.METHODS. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the addition of therapeutic vaccines (ALVAC-HIV [vCP1452] or ALVAC-HIV and Remune) to ART initiated during acute infection could increase the probability of having a plasma viral load </=1000 HIV-1 RNA copies/mL 24 weeks after planned discontinuation of ART.RESULTS. All 79 randomized subjects completed the immunization schedule, and 78 discontinued ART with no major safety concerns. After immunization, subjects in the vaccine study arms had significantly increased HIV-1-specific CD4(+) and CD8(+) T cell responses, by interferon- gamma enzyme-linked immunospot assay, compared with those in the placebo study arm. Overall, 17.7% of subjects had </=1000 HIV-1 RNA copies/mL 24 weeks after discontinuation of ART, with no significant difference between the vaccine study arms and the placebo study arm (15.4% vs. 22.2%; difference, -6.8% [95% confidence interval, -26.8% to 10.0%]; P=.54).CONCLUSION. Therapeutic immunization and ART, compared with ART alone, generated HIV-1-specific cellular immunity but did not lead to better virological control of HIV-1 24 weeks after discontinuation of ART. Our trial design appears to be feasible and safe for testing future immune-boosting strategies.

AIDS Vaccines↗

Placental transfer of IgG antibodies against Haemophilus influenzae type b capsular polysaccharide in Brazilian term and preterm newborns.

Placental transfer of antibodies to polysaccharide antigens is still a controversial subject. The incidence of invasive Haemophilus influenzae type b (Hib) infections is high in countries where the vaccine has not been included in routine immunization schedules. In the present work, we proposed to evaluate the natural immune response to Hib capsular polysaccharide in term and preterm Brazilian newborns and their respective mothers. Although the means, medians, and ranges of antibody titres in paired maternal and cord sera from preterm neonates were similar, the maternal levels were slightly higher than the cord levels and a poor correlation between these levels was verified. Term neonates showed similar antibody levels to those of their respective mothers and a very significant correlation between these levels was observed.

Antibodies, Bacterial↗

Suppression of local intestinal immunoglobulin A immune response to cholera toxin by subcutaneous administration of cholera toxoids.

Cholera toxin has been shown to modulate immune responses, generally producing enhancement when administered simultaneously with antigen and suppression when administered a day or more earlier. In a previous study using chronically isolated ileal loops in rabbits, we found that two subcutaneous (s.c.) "priming" and "boosting" doses of biologically active cholera toxin suppressed the local intestinal immunoglobulin A response to intraloop doses of cholera toxin. In the study reported here, two different biologically inactive but antigenically intact cholera toxoids, glutaraldehyde toxoid and choleragenoid, where administered s.c. by the same immunization schedule as for toxin in the earlier experiment. Suppression of local immune response to intraloop cholera toxin as compared with animals receiving no s.c. inoculations was again found. The results suggest that in this model suppression was immunological (mediated by an immunological mechanism) rather than toxigenic (mediated by biological activity of cholera toxin). In addition, the occurrence of suppression of local intestinal immune response after systemic immunization suggests that suboptimal protection against enteric infections could occur after s.c. vaccination.

Antibody Formation↗

A "high-tech," "soft-touch" immunization program for members of a Medicaid managed care organization.

Immunization rates among the very poor are critically low. The solution to improving rates requires technological tracking of immunizations linked to extensive home visiting outreach services as well as physician and member support services to increase compliance with recommended immunization schedules. This paper describes the development and implementation of a comprehensive immunization program which incorporates these strategies for members of a Medicaid managed care organization. Analysis of preliminary data provides some indication of the value of the tracking system and the effectiveness of incentives and home visiting on member compliance with immunizations.

Accounting↗

Immunological memory: the role of B cells in long-term protection against invasive bacterial pathogens.

Protein-polysaccharide conjugate vaccines that protect against Haemophilus influenzae type b (Hib), serogroup C Neisseria meningitidis, and multiple capsular serotypes of Streptococcus pneumoniae have had a major impact on invasive bacterial disease in childhood when incorporated into routine infant immunization schedules. However, effectiveness data from the United Kingdom suggest that primary infant immunization alone may not be associated with long-term protection. Both immunological priming and antibody persistence are important aspects of long-term protection induced by these vaccines. An improved understanding of the immunobiology of the B-cell response to these vaccines may direct development of immunization strategies that provide sustained protection.

Antibodies, Bacterial↗

Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients.

Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B-cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous mono-clonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I-III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-gamma and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9-5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19+ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.

Adult↗

[The development of the anti-phospholipase A2 antibody response in horses inoculated with venom for the production of polyvalent antisnake serum in Costa Rica].

The development of antibody response against phospholipase A2 activity of Bothrops asper venom was studied in a group of adult and healthy horses used in the production of the polyvalent antivenom at the Instituto Clodomiro Picado. Simultaneously, the general condition of the animals during the immunization schedule was also studied. There was a great individual variability in the immune response, although most of the horses studied reached the highest neutralizing titer after injection of doses of venom of 30 mg and 50 mg. On the other hand, in horses that had been previously immunized and were infected for a second immunization, the highest antibody titer was observed 16-22 days after inoculation. There were only mild alterations in the general condition of the horses as a consequence of venom inoculation. However, local abscesses, fistulae and fibrosis were observed at the site of venom injection. On the basis of the conspicuous individual variability observed, it is proposed that the immune response in horses used in the production of antivenom must be evaluated on individual basis, instead of working with pools of serum samples.

Animals↗

Production of monoclonal antibodies to squamous cell carcinoma antigens.

For therapeutic or diagnostic use of monoclonal antibodies in clinical oncology, high-affinity IgG antibodies to tumor-associated antigens have to be generated. In order to find out by what immunization schedule the chance to generate such antibodies is increased, we evaluated three different immunization protocols with and without attempts to induce tolerance to common tissue antigens. Mice were immunized either (1) by repeated intraperitoneal injections, (2) by a single intrasplenic injection, or (3) by an intraperitoneal injection followed by an intrasplenic booster. Whereas a single intrasplenic immunization resulted in low-affinity antibodies to tumor-associated antigen, high-affinity antibodies were generated with the other two protocols, although at a lower frequency. No benefit was seen from tolerance induction. The intraperitoneal/intrasplenic protocol was found to be superior over the other protocols because of minimal antigen dose and immunization time, as well as a higher frequency of hybridoma formation.

Animals↗

Booster vaccination against diphtheria and tetanus in man. Comparison of three different vaccine formulations--III.

Adverse reactions and antibody levels were compared following a booster vaccination of 177 Danish military recruits with a plain, an aluminium hydroxide (0.5 mg Al per human dose, HD) and a calcium phosphate (0.25 mg Ca per HD) adsorbed diphtheria-tetanus (D-T) vaccine. The calcium phosphate adsorbed vaccine was given in a HD of 3 Lf of D and T toxoids and proved to be of equal efficacy as the aluminium hydroxide adsorbed vaccine which was injected in a dose containing twice the antigen amount. The calcium phosphate vaccine caused fewer adverse reactions than the one adsorbed to aluminium hydroxide. The plain vaccine (6 Lf per HD of D and T toxoid) had the highest efficacy with a similar low occurrence of adverse reactions as the calcium phosphate adsorbed vaccine. Potency assays in mice were in accordance with these immunogenicity results in man if a two dose immunization schedule was followed, but not if the vaccines were compared after a single immunization as requested by the procedure for potency testing according to current WHO and European Pharmacopoeia requirements. Both of the adsorbed vaccines primed mice for specific IgE antibody formation. This could be detected after a second immunization with either of the adsorbed vaccines or with the plain D-T vaccine. Also in humans, immunization with the plain vaccine boosted specific IgE formation to a detectable level. This may be ascribed to adjuvant priming during the primary vaccination series some 20 years previously.

Adolescent↗

Prevention of hepatitis B by immunization of the newborn infant--a long-term follow-up study in Stockholm, Sweden.

In order to assess the present hepatitis B immunization program in Stockholm, Sweden, 212 children of HBsAg carrier mothers were followed up 2-9 years after birth. In babies of HBeAg-positive mothers a combined passive and active immunization schedule with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine was used. Among 25 children to such mothers, 1 HBsAg carrier and 5 children with asymptomatic seroconversion were found. To newborns of HBeAg-negative/anti-HBe-negative mothers, only vaccine was given. Among 15 such children, no HBsAg carrier (but 1 child with an asymptomatic seroconversion) was found. In babies of HBeAg-negative/anti-HBe-positive mothers, immunization was withheld between 1983 and 1987. Among 90 such children, 1 HBsAg carrier and 8 asymptomatic seroconversions were detected. After 1987, newborns in this group were vaccinated whereafter 3 asymptomatic seroconversions were found among 82 children. We conclude that in low prevalence areas a screening program for HBsAg should be offered to pregnant women originating from hepatitis B endemic regions, since immunoprophylaxis gave long-term protection to most children at risk. Children born to HBeAg-positive mothers should receive vaccine in combination with HBIg, whereas for children of mothers lacking HBeAg, vaccination only seems sufficient, at least if a rapid vaccination schedule is used.

Carrier State↗

[Vaccinations for traveler child].

Each year, half a million of children leave France to travel towards countries south or east of the European Union, sometimes in poor sanitary conditions. In order to propose essential or useful immunizations for these trips, the current synthesis will allow the practitioner to insure that the routine French immunization schedule has been followed, and to complete it if needed, to protect the child according to the epidemiological situation in the visited area, to try to reduce the limitations of the immunization of the traveler child. In case of emergency, or close departure, it may be useful to follow an accelerated schedule of the last minute, and, sometimes, to immunize traveler children with a chronic disease. Informations on Internet sites useful for the knowledge of current infectious risks in the destination country are also provided.

France↗

Childhood immunization: one HMO's experience in benchmarking and improving plan performance.

In 1994, Health Net initiated a childhood immunization campaign and research project to improve health plan member immunization rates by motivating and educating parents of children 20-32 months old as to the importance of fully immunizing their child. The findings indicate that 88 percent of those parents with children who were not fully immunized believed their child had been fully immunized by age two. This lack of awareness may explain the unreliability of self-reported immunization status. Future immunization campaigns must include ongoing member reminder systems, educate members as to the immunization schedule, and must take into consideration the barriers, real and perceived, that block full immunization.

California↗

Epidemiology of poliomyelitis in a slum of Bombay.

A disease prevalence and immunization coverage survey in a typical slum in Bombay in the year 1988 revealed 93 children with residual poliomyelitis amongst 14,439 children below 9 years of age, indicating high (33.0/100,000 population) annual incidence of poliomyelitis. Only 62 (66.6%) of these 93 lame children sought admission in hospital during the acute phase of illness. The high incidence was attributed to a low immunization (OPV) coverage level in the most vulnerable age group. The immunization coverage for 3 doses of oral polio vaccine below 2 years of age was 43.5%. A large number of children were not commencing their immunization schedule at the right age. The survey indicated a poor "community participation" in the immunization programmes due to a poor "health awareness".

Child↗

Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice.

Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, [BR----AKR], as well as syngeneic marrow cells, [AKR----AKR], showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, [B10----AKR], [B10.AQR----AKR], [B10.A(4R)----AKR], or [B10.A(5R)----AKR], were almost completely unresponsive in DTH and antibacterial immunity. However, when [B10----AKR] H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type.

Animals↗

Four years of measles elimination in the Czech Socialist Republic.

In 1982, Czechoslovakia succeeded in eliminating measles infection throughout the country. The paper describes the strategy of the measles immunization program following its introduction in 1969, showing it to reflect the objective epidemiological situation as revealed by the regular immunological surveys carried out in a broad population sample. As it turned out, decisive for achieving and maintaining a permanent measles elimination in the country was the introduction of second vaccination into the regular immunization schedule. Since 1982, its timing of is from 6 to 10 months after primary immunization. Over the 4-year period between 1982 and 1985, confirmed measles occurred only sporadically in the CSR, 115 cases altogether, and of these as many as 67 were classified as imported or their immediate contacts (38 measles patients were tourists from abroad). Of these 115 measles cases, 52 had had vaccination prior to acquiring the disease, 46 were individuals who had never before been vaccinated and in the remaining 17 patients no vaccination data were available. The vaccine failures, at least in 18 cases, could have been explained by the primary immunization prior to reaching 15 months of age. According to the estimates, at least 670 thousand cases of measles, 470 deaths, 100 thousand complications and some 33 thousand hospitalizations had been averted between 1972 and 1985 on the territory of CSR as a result of the introduction of the measles immunization program in Czechoslovakia.

Adolescent↗