Immunization schedules for the new human diploid cell vaccine against rabies

The records of 340 patients treated surgically over the 20 year period 1950 through 1969 at this clinic for primary epidermoid carcinoma of the anterior two-thirds of the tongue were reviewed to evaluate the effectiveness of elective versus therapeutic radical neck dissection in their treatment. There has been a change in the clinical presentation of this disease, with more people presenting at an earlier stage, with a smaller primary lesion and fewer cervical node metastases. The over-all survival rate has shown a marked improvement to 69 per cent at five years. The proportion of women afflicted has increased. The status of the cervical nodes is a major prognostic factor, the determining five year survival rate being reduced from 78 to 26 per cent if the nodes are metastatically involved. It cannot be directly proved that removal of occult metastasis to the neck by elective radical neck dissection before nodes are clinically detectable leads to a better survival rate partly because the two groups being compared are selected and not randomly assigned. However, the marked tendency for carcinoma of the tongue to metastasize regionally at some time in its course, the significant error in clinical evaluation of the neck, the significant conversion of clinically negative nodes to positive in patients not treated with radical neck dissection, the poor prognosis after treatment of conversion from clinically negative into positive and the fact that more than half of the deaths are due to uncontrolled disease of the neck alone, make us strongly favor the principle of elective radical neck dissection to enhance the survival time in the group of patients without clinical evidence of nodal involvement. With current surgical expertise, the mortality and morbidity rates of simultaneous radical neck dissection are low, and the potential benefit of the procedure outweighs its potential risks. Obviously, elective radical neck dissection, if beneficial, would most likely be so in patients with the highest likelihood of having occult metastasis.     

Immunization with hybrid hepatitis B virus core particles carrying circumsporozoite antigen epitopes protects mice against Plasmodium yoelii challenge

The hepatitis B virus nucleocapsid antigen (HBcAg) was investigated as a carrier moiety for circumsporozoite protein (CS) repeat B cell epitopes of the rodent malaria agent Plasmodium yoelii. A vector expressing a hybrid gene coding for the dominant CS repeat epitope (QGPGAP)4 was constructed and transformed into avirulent Salmonella typhimurium. The resulting hybrid HBcAg-CS polyproteins were purified from recombinant Salmonella typhimurium. They purified as particles and displayed HBc as well as P. yoelii CS antigenicity. To investigate immunogenicity and protective efficacy, BALB/c mice were immunized with the hybrid HBcAg-CS particles. Immunization resulted in high titered antinative CS serum IgG antibody litres. BALB/c mice immunized with hybrid HBcAgCS particles were between 90-100% protected against subsequent P. yoelli challenge. Protective immunity persisted for a minimum of three months. These data confirm the previous suggestion (Sch?del et al., 1994), that hybrid HBcAg particles could become a useful component of future human malaria vaccines.     

Immunization against learned helplessness in man.

Immunization against learned helplessness has been found in dogs and rats; the present experiments tested for the same effect in humans. In Exp I, 38 college students were divided into 4 groups. A helplessness control group received no immunization training, whereas 3 other groups received either a 0, 50, or 100% schedule of success on a series of discrimination problems. All groups were then given insoluble problems and were subsequently tested on a human shuttle box. An immunization effect against helplessness was produced; the 50% immunization schedule produced performance significantly superior to the helplessness control and 0% groups. The 100% group failed to produce the immunization effect. Exp II with 45 Ss involved a partial replication of the 1st experiment, but anagram solutions were used as the test task. Also, control groups based on the triadic design were included in Exp II. Results for the 2nd experiment essentially paralleled the results from Exp I. Immunization effects were shown following a 50% schedule but not following either 0 or 100% immunization schedule. These findings lend substantial support to the stimulus–response explanation of helplessness phenomena over the expectancy-of-independence explanation. Implications of the study for the helplessness model of depression and for strategies in clinical therapy are also discussed. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assay of oral vaccination of dogs against rabies in Tunisia with the vaccinal strain SADBern

The possibility of immunizing dogs orally against rabies, using SADBern, an attenuated strain, was tested on dogs in the field in Tunisia. This strain induced high neutralizing antibody titres and conferred to all vaccinated dogs total resistance against a challenge with a Maghrebian strain. However, an excretion of virus of vaccinal origin was observed in one dog, hampering the use of SADBern in dogs. Nevertheless, this work demonstrates for the first time that dogs in developing countries, especially those which are inaccessible to parenteral vaccination, could be efficiently immunized against rabies by the oral route.     

Human contamination by baits for vaccinating foxes against rabies in France

During 1992 and 1993, 4.4 million of baits have been distributed in France over 121,381 km2 for vaccinating foxes against rabies. Phone calls and visits addressed to the local veterinary authorities and to the centres for human antirabies treatment have been recorded according to an appropriate questionnaire. 70 persons declared to have found and sometimes to have touch a bait, 38 of them received a antirabies treatment. Only 9 children (less than 10 year old) handled a bait. Activities that led to find a bait have been: walking in the countryside or hunting (50% of cases), gardening or playing in the garden or near home (35%) and farming (13%). Often dogs were the first to discover the baits and led to a contact of humans with the vaccine in 54% of cases. No casualty occurred. The frequency of these reports decrease by 80% during the period which is considered to be the result of a better information and awareness of the public.     

Efficacy of the first oral vaccination against fox rabies in Slovenia

Fox population reduction was the first measure undertaken to control rabies in foxes, but this proved unsuccessful. The promising results of oral immunisation of foxes against rabies in some European countries encouraged the authorization of the first rabies vaccination of foxes in the field in Slovenia, in October 1988. In the present study, intervention analysis is used to evaluate the results of this vaccination campaign. The analysis took into account the cyclic nature of fox rabies and the possible effects of variability in the fox carcass submission rate. The results confirmed the decrease in fox rabies after the launch of the vaccination campaign. The reduction was independent of both cyclic oscillations in fox rabies and variability in carcass submission rate, thus indicating a positive net effect of the vaccination.     

Immunization against leptospirosis: vaccine trials with heat-killed whole cell and outer envelope antigens in hamsters

Heat-killed whole cell and outer envelope antigens prepared from homologous virulent and avirulent strains of Leptospira serotypes canicola and pomona were evaluated for protecting hamsters against experimental leptospirosis. The heat-killed bacterins proved at least as effective as the outer envelope antigens, or more so, in providing protection against death and infection, and they are easier and more economical to prepare.     

Immunization with virus-modified tumor cells

Direct infection of tumor cells with viruses transfering protective or therapeutic genes-a frequently used procedure for production of tumor vaccines in human gene therapy-is often limited by the number of tumor cells that can reliably be infected, as well as by issues of selectivity and safety. In this review, we describe an efficient, selective, and safe way of infecting human tumor cells with a natural virus with interesting pleiotropic immune stimulatory properties, the avian paramyxovirus Newcastle disease virus (NDV). Advantages of this virus are its good cell-binding properties, its selective replication in tumor cell cytoplasm, which is independent of cell proliferation, and its relative safety. Most important for its use as an adjuvant in human cancer vaccine are its ability to introduce T-cell costimulatory activity, to prevent anergy induction, and to induce locally chemokines (eg, RANTES, IP-10) and cytokines (eg, interferon alpha, beta [IFN-alpha, beta] and tumor necrosis factor-alpha [TNFalpha]) that affect T-cell recruitment and activation. A further development consists of attachment-via NDV-derived hemagluttinin-neuraminidase (HN) membrane-anchoring molecules-of universal defined bispecific reagents such as T-cell-activating anti-CD28 antibodies. Finally, we summarize the status of our clinical studies with the autologous virus modified live cell vaccine (ATV)-NDV.     

Measles virus-induced autoimmune reactions against brain antigen

Recovery from viral infection is a result of very complex interactions between specific and nonspecific immune reactions and the infectious agent. A variety of immune mechanisms are undoubtedly important factors in this event and operate together in overcoming the infectious process. However, despite much available information about these viral defense mechanisms, it has proved remarkably difficult to assign a determinative role in vivo to any single antiviral immunological mechanism in recovery from a single viral disease, particularly since the immune response to the virus itself may frequently contribute to the pathology of the disease. Furthermore, if virus-induced immune responses are also directed against normal host components, this may set the stage for an autoimmune disease. In this context acute measles encephalomyelitis is of interest since in this disease autoimmune reactions against brain antigens have been observed and considered of pathogenetic importance. In this short review, virological and immunological findings of measles virus infections in a rat model in relation to autoimmune reactions will be presented and the mechanisms by which measles virus may alter host reactivity against self-antigens discussed.     

Immunization against the observational conditioning of snake fear in rhesus monkeys.

Examined the effects of extensive prior exposure to snakes on subsequent observational conditioning of snake fear in 24 rhesus monkeys (Macaca mulatta). Three groups of Ss were given 1 of 3 kinds of pretreatment: (1) An immunization group spent 6 sessions watching a nonfearful monkey behave nonfearfully with snakes; (2) a latent inhibition group spent 6 sessions by themselves behaving nonfearfully with snakes with total exposure time to snakes equal to that for the immunization group; and (3) a pseudoimmunization group spent 6 sessions of observational conditioning in which they watched fearful monkeys behave fearfully with snakes. When subsequently tested for acquisition of snake fear, the pseudoimmunization and latent inhibition groups showed significant acquisition, but 6 out of 8 Ss in the immunization group did not. Thus, it seems that for a majority of Ss, prior exposure to a nonfearful model behaving nonfearfully with snakes can effectively immunize against the subsequent effects of exposure to fearful models behaving fearfully with snakes. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human diploid cell culture rabies vaccine (HDCV) and purified chick embryo cell culture rabies vaccine (PCECV) both confer protective immunity against infection with the silver-haired bat rabies virus strain (SHBRV)

The demonstration of extensive differences in the antigenic makeups of the silver-haired bat rabies virus (SHBRV) and canine rabies virus (COSRV) strains raised concerns as to whether current licensed rabies vaccines are sufficiently protective against SHBRV. NIH mouse protection test results show that both the human diploid cell culture rabies vaccine (HDCV) and the purified chicken embryo cell rabies vaccine (PCECV) protected against lethal infection with SHBRV as well as the canine rabies strain COSRV. However, in this investigation, the potencies of both vaccines in mice were found to be significantly higher for COSRV than for SHBRV. The in vivo protection data are confirmed by in vitro virus neutralizing antibody (VNA) test results which demonstrate that mice immunized with HDCV or PCECV develop significantly higher VNA titres against COSRV than against SHBRV. In contrast, VNA tests of sera from individuals immunized with HDCV or PCECV showed that humans, as opposed to mice, develop significantly higher VNA titres against SHBRV than against COSRV. These data suggest that HDCV and PCECV will protect humans against infection with the silver-haired but rabies virus strain in addition to canine rabies virus strains.     

Failure of protection induced by a Brazilian vaccine against Brazilian wild rabies viruses

This report shows that the SMB vaccine currently used in Brazil for human immunisation provides different degrees of protection in mice, depending on the rabies virus strain used as challenge. Using the NIH and Habel potency tests to evaluate the protective activity of rabies vaccine, we observed that vaccinated mice showed a higher resistance to a challenge with a fixed rabies virus (CVS-Challenge Virus Strain). The vaccine potency using the Habel or NIH tests was respectively > 6.4 (log 10) and 1.0 (Relative Potency-RP) when the fixed rabies virus was used for challenge, and from 2.9 to 4.3 (log 10) or 0.13 to 0.8 (RP) when different wild rabies viruses were used for challenge. The presence of virus neutralising antibodies (VNA) could not explain the differences of susceptibility after vaccination, since sera of vaccinated animals had similar VNA levels against both fixed and wild strains before virus challenge (respectively, 5.6 +/- 0.24 and 5.0 +/- 0.25 IU/ml of VNA against the fixed rabies virus and the 566-M strain of wild rabies virus in sera of mice vaccinated with 0.2 units of vaccine). Only cell-mediated immunity parameters correlated with the protection induced by vaccination. The IFN gamma titers found in sera and brain tissues of animals challenged with CVS strain were higher (from 36.7 +/- 5.7 to 293.3 +/- 46.2 IU/ml) than those found in mice challenged with 566-M virus strain (from 16.7 +/- 5.8 to 36.7 +/- 5.8). The proliferation index of spleen cells obtained with CVS stimulation reached a maximal value of 15.1 +/- 0.7 while spleen cells from vaccinated mice stimulated with 566-M virus failed to proliferate. The implications of these data in human protection by vaccination are discussed.     

Problems associated with rabies preexposure prophylaxis

With the rabies vaccine presently available for preexposure prophylaxis, 20% of all individuals do not have seroconversion following routine immunizations, and 5% are allergic to this vaccine. Two experimental rabies vaccines of cell culture origin offering greater purity and potency were evaluated by means of a double-blind experiment. Thirty-one volunteers who did not have seroconversion or who were allergic to duck embryo rabies vaccine received rabies vaccine produced in either human diploid cell culture (WI-38), or hamster kidney-cell culture. All volunteers had seroconversion within 14 days of receiving a single injection of other experimental vaccine. Clinical side effects were only minor.     

Vaccination against Haemonchus contortus with denatured forms of the protective antigen H11

As part of a systematic examination of the protective epitopes on H11, groups of sheep were vaccinated with preparations of purified H11 used untreated (group A), or progressively denatured (linearized) by incubation with sodium dodecyl sulphate (SDS) (group B) or by boiling with SDS in the presence of dithiothreitol (group C). All the sheep developed antibodies which bound to the untreated H11. When challenged with 10,000 infective larvae of Haemonchus contortus the mean levels of protection relative to the mean values for adjuvant controls were 99.8%, 85% and 79% for faecal egg counts and 95%, 79% and 54% for worm burden at post-mortem for groups A, B and C respectively. The H11-specific antibodies inhibited the microsomal aminopeptidase activity of H11 in vitro up to 80%. The levels of inhibition by sera from individual animals correlated with levels of protection with r2, of 0.69-0.87.     

Immunization against experimental trichinosis using T. spiralis larvae and hydatid fluid antigens

Immunization of mice against T. spiralis infection using T. spiralis larval glycoproteins as homogenous antigen and crude hydatid fluid as heterogenous antigen showed a marked reduction in larvae burden and a significant rise of serum IgE in immunized mice infected with T. spiralis larvae as compared with control group. More reduction was observed with immunization with homogenous T. spiralis larval antigen compared with heterogenous hydatid fluid antigen. The reduction in larval burden with rise of serum IgE begins after the third week of immunization.