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.

Adjuvants, Immunologic↗

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Treatment of relapsing chronic infections of the respiratory tract. A comparative study of the effectiveness of non specific immunotherapy with the immunoadjuvant P40 and of vaccinotherapy.

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Adjuvants, Immunologic↗

PubMedDate not supplied

Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine.

OBJECTIVES: To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. STUDY DESIGN: We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. METHODS: We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. RESULTS: p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. CONCLUSION: Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.

AIDS Vaccines↗

PubMedDate not supplied

Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.

OBJECTIVES: To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. METHOD: The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). RESULTS: Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. CONCLUSION: These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.

AIDS Vaccines↗

PubMedDate not supplied

Human papillomavirus-16-E7 oncoprotein enhances the expression of adhesion molecules in cervical endothelial cells but not in human umbilical vein endothelial cells.

OBJECTIVES: E7 is one of the oncoproteins encoded by human papillomavirus-16 (HPV-16), the major etiologic factor responsible for cervical cancer. Human papillomavirus-16-E7 expressed by human uterine cervix carcinoma cells is also released in the extracellular compartment where it induces immune suppression. We investigated whether E7 was also responsible for the enhanced endothelial adhesiveness required in cancer progression. STUDY DESIGN/METHODS: We treated cervical microvascular endothelial cells (CrMVEn) and human umbilical vein endothelial cells (HUVEC) with E7, tumor necrosis factor-alpha (TNF-alpha), and hydrogen peroxide (H2O2) and measured the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by fluorescent-activated cell sorter analysis. RESULTS: E7 strongly induced the expression of E-selectin, ICAM-1, and VCAM-1 in CrMVEn, but not in HUVEC. Tumor necrosis factor-alpha further increased the endothelial expression of adhesion molecules in CrMVEn. Hydrogen peroxide pre-treatment resulted in an enhanced ICAM-1 and a decreased E-selectin and VCAM-1 expression. We also show indirect effects when endothelial cells were stimulated with the supernatant of E7-pretreated macrophages. CONCLUSIONS: These results show that HPV-16-E7 oncoprotein strongly induces adhesion molecules expression in organ-specific endothelial cells.

Cell Adhesion Molecules↗

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[Purification of a protein characteristic of pathogenic strains of "Beauveria tenella" (author's transl)].

Purification of the protein which in immunoelectrophoresis is responsible for the precipitation are characteristic of the pathogenic strains, can easily be obtained by isoelectrofocalisation: two protein fractions are isolated. These differ in their isoelectric points and in their relative electrophoretic migration coefficients in polyacrylamide gel, but exhibit the same antigenic specificity.

Animals↗

PubMedDate not supplied

Evaluation of anti-Listeria monocytogenes antibodies by ELISA.

A new ELISA test using the purified Listeria monocytogenes-derived antigen LM 84 Ag is described together with its application in the diagnosis of listeriosis. Fifty-seven human sera were titrated by the ELISA and the complement fixation method and compared for specificity and sensitivity. The problem of possible cross-reactions with other antigens is discussed.

Antibodies, Bacterial↗

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An experimental and clinical study of immunocompetence and immunostimulation in breast cancer.

Two hundred and seven patients aged from 37 to 65 years with noninflammatory breast cancer treated by surgery without radiation were studied over a ten year period with a view to forecasting the prognosis on the basis of the immune status and treatment. The immunocompetence or immune status was studied in 121 patients by in vitro and in vivo pre and post-surgical skin tests. The immunostimulation or restoration of the immune status was conducted by the P 40 immunomodulator from the Pasteur Institute: in an experimental study whose results are based on modified Huggins model and take in to account the survival rate and the evaluation of tumor growth; in a subgroup of 86 patients, demonstrating that immunostimulation is effective in low-scores, improves tolerance to chemotherapy and increases the six year survival rate in high risk low-score patients. The results are encouraging enough to propose improving the survival rate in a prospective clinical study of early breast cancer treated by local and regional means using a protocol incorporating an immunostimulation based on the existing immunocompetence with interferon-induced reconversion of the target cells in the hope of specific stimulation.

Adjuvants, Immunologic↗

PubMedDate not supplied

Studies on the immunostimulating and anti-tumour activity of a fraction isolated from Corynebacterium granulosum.

The immunostimulating activity of the anaerobic corynebacteriae is well documented. Fractions isolated from while cells have not been much investigated. We have reported that the immunostimulating activity is present in fractions isolated from Corynebacterium granulosum. A few fractions have shown anti-tumour activity in grafted tumours in mice. One of these fractions (P 40) has been investigated in more detail, since it proved to be inhibitory when administered after grafting of the non-syngenic P 815 tumour in mice.

Animals↗

PubMedDate not supplied

Studies on the antigenic structure of tetanus toxin.

The isolation and purification of split-products from tetanus toxin after freezing is reported. Antigenically defective and non-defective fragments exhibiting reduced molecular weights with respect to that of intact toxin were investigated as to their biological and immunological properties. The results obtained are discussed in relation to other data from the literature.

Animals↗

PubMedDate not supplied

Immunological investigation and immunotherapy in patients operated on for breast carcinoma.

The tumor-host relationship is an essential factor in the onset, development, and recovery from malignancies. A basic consideration in the treatment of cancer patients must therefore be to understand this relationship and attempt to modify it in order to favor the host. We here discuss the results of a study of the immunologic status of 91 breast cancer patients. The use of a battery of tests with five subcutaneous hypersensitivity antigens allowed us to detect some differences in the immunological profiles of patients with or without lymph node involvement. The effect of an immunostimulant fraction prepared from Corynebacterium granulosum, P40 is also analyzed. This fraction significantly modifies tumoral recurrence in DMBA-induced mammary cancers in the Sprague Dawley rat, causes regression of mammary permeation nodules following in situ injection and modifies the cutaneous reactions of one-half of the anergic breast cancer patients although regular re-challenge is still necessary.

Adenocarcinoma↗

PubMedDate not supplied

[Humoral and cellular immunologic reactions in various forms of chronic psychiatric diseases].

Studies on the status of the immune system in mental disorders have mostly provided contradictory results. For example, some authors have reported dramatic increases of immunoglobulin G in schizophrenic patients, and others a decrease of immunoglobulin G in the same patients. This prompted us to undertake a study on a large cohort of psychiatric patients (120 schizophrenics, 30 manic-depressives, 8 epileptics, 48 cases of Alzheimer and vascular dementia, 23 cases of alcoholic dementia, 14 cases of childhood psychosis, 47 encephalopaths, and 21 chronic alcoholics), all chronically hospitalized. Plasma antitetanus antibodies were assayed in 238 previously immunized patients, the tuberculin test was performed on 302 patients, and the candidine test on 287 patients. Furthermore, 21 patients had an antitetanus vaccine booster injection with antibodies assayed before the injection and one month later, and 31 patients had 2 tuberculin tests with a year or more between them. The results show no major abnormal immune disorders in the patients. Nevertheless some particular features have been found. The first is a very significant relation between the age and the weakness of the immune defences. The second is a large scattering of the blood tetanus antibodies titers in schizophrenic patients, specially in the paranoid subgroup (20.6% of abnormally high or low titers). And the third is the existence of inpredictable variations in the responses when stimulations, or tests, are repeated. These results can raise the hypothesis of a state-dependent component of the immune response in mentally ill patients, but further in, depth studies are needed for better understanding the nature of our findings.

Adult↗