Further characterization of stimulus interaction of cat carotid chemoreceptors

Cellular as well as humoral immune reactivity were studied in healthy young (< 30 years; n = 12) and older (> 65 years; n = 12) individuals before as well as 1 month after immunization with a trivalent whole virus influenza vaccine. Before vaccination, peripheral blood mononuclear cell proliferation in response to in vitro stimulation with each of the virus strains was low in both groups. No antibodies against either the H1N1 or the B strain were found in most individuals, while 91% of the young and 75% of the elderly persons had low but protective antibody titres to the H3N2 strain. Vaccination led to a significant enhancement of peripheral blood mononuclear cell reactivity to all three influenza strains in both age groups. However, there was a significant difference in the humoral immune response between the groups. While there was a vigorous antibody response to all three vaccine strains among young persons, protective titres against the H1N1 and the B strains were only just reached in the old. In contrast, antibody production to the H3N2 strain was most abundant in the majority of elderly individuals, leading to significantly higher titres in the old than in the young group. In conclusion, the results demonstrate the preferential induction of antibodies to one particular influenza strain despite equal T cell recruitment to all vaccine strains in healthy aged individuals after immunization with a trivalent influenza vaccine. Our findings underline the complexity of immunological alterations to be expected after vaccination in healthy elderlies.     

The importance of MHC-I and MHC-II responses in vaccine efficacy against lethal herpes simplex virus type 1 challenge

To investigate the importance of major histocompatability complex (MHC) class I- and MHC class II-dependent immune responses in herpes simplex virus-1 (HSV-1) vaccine efficacy, groups of beta 2% (MHC I-) and Ab% (MHC II-) mice were inoculated with various vaccines, and then challenged intraperitoneally with HSV-1. Following vaccination with either live avirulent HSV-1, expressed HSV-1 glycoprotein D (gD), or a mixture of seven expressed HSV-1 glycoproteins (7gPs), Ab% (MHC-II-) mice developed no enzyme-linked immunosorbent assay (ELISA) or neutralizing antibody titres. In contrast, significant ELISA and neutralizing antibody titres were induced in beta 2m% (MHC-I-) mice by all three vaccines. The neutralizing antibody titres were similar for all three vaccines, but were only approximately 1/4 to 1/3 of that developed in C57BL/6 (parental) mice vaccinated with the same antigens. All three vaccines protected 100% of the wild-type C57BL/6 mice against lethal challenge with 2 x 10(7) plaque-forming units (PFU) of HSV-1. The live virus vaccine and the 7gPs vaccine also protected 80% of the beta 2m% mice against the same lethal HSV-1 challenge dose. In contrast, in Abo/o mice, none of the vaccines provided significant protection against the same lethal challenge dose of HSV-1. However, at a lower challenge dose of 2 x 10(6) PFU, all three vaccines protected 70-80% of the vaccinated Ab% mice (compared to only 10% survival in mock vaccinated controls). Thus, vaccination provided some protection against lethal HSV-1 challenge in both beta 2m% and Ab% mice; however, the protection was less than that seen in the parental C57BL/6 mice. In addition, Ab% mice were less well protected by vaccination than were beta 2m% mice. Our results suggest that (1) both MHC-I and MHC-II are involved in vaccine efficacy against HSV-1 challenge; (2) both types of responses must be present for maximum vaccine efficacy: and (3) the MHC-II-dependent immune response appeared to be more important than the MHC-I-dependent immune response for vaccine efficacy against HSV-I challenge.     

beta-Carotene accumulation in mouse tissues and a protective role against lipid peroxidation

Recent population-based efficacy trials of the synthetic malaria vaccine SPf66 have shown restricted, if any, clinical protection against Plasmodium falciparum infection. Despite the well-established role of antibodies in effector responses against asexual blood-stage malaria parasites, the titres of anti-SPf66 IgG antibodies do not correlate with the ability of sera from vaccine recipients to inhibit parasite growth in vitro nor with partial clinical protection which could be detected in some trials. Qualitative or functional parameters of SP66-induced antibody responses, such as IgG subclass composition and affinity, may be more predictive of clinical protection against malaria than quantitative estimates of antibody concentration or titre. Since these parameters are readily estimated by laboratory techniques currently available, and may be modulated by changes in vaccination protocols and by the use of different adjuvants, a better understanding of qualitative antibody responses induced by SPf66 and other asexual blood-stage malaria vaccine candidates, and of their relationship with clinical protection in vivo, is urgently needed for the improvement of currently used immunization schedules.     

Safety and immunogenicity of a new influenza vaccine grown in mammalian cell culture

In a phase I safety and immunogenicity study, 112 healthy adult volunteers were randomly allocated to receive a new bivalent (A/Texas/36/91[H1N1-like], B/Harbin/7/94) split virion influenza vaccine propagated in Madin-Darby Canine Kidney cell culture or an identical vaccine manufactured using currently licensed egg propagated virus technology. Soreness at the injection site was common but generally mild (75% of the cell culture-derived vaccine group and 62.5% of the egg-derived vaccine group; p = not significant). General reactions were less common; headache was the most frequently reported adverse effect (26.8 and 30.4%, respectively; p = not significant). Geometric mean haemagglutination inhibition titres post-immunization against the A/Texas strain were 1012 reciprocal dilution in the cell culture-derived vaccine group and 790 in the egg-derived vaccine group; against the B/Harbin strain titres were 420 and 447, respectively (all comparisons, p = not significant). It is concluded that the cell culture-derived split virion influenza vaccine is safe and immunogenic in healthy adult volunteers.     

Babesial antibody dynamics after cattle immunisation with live vaccines, measured with an indirect immunofluorescence test

The efficacy of vaccination of Argentinean cattle against babesiosis and anaplasmosis using live immunogens was tested to detect specific antibodies in samples obtained about 60 days after vaccination. Under these conditions a higher than expected proportion of cattle failed to show antibodies against Babesia bigemina. Therefore, a study was designed to evaluate if this failure was due to insensitivity of the routine test to detect antibodies to B. bigemina or to lack of infectivity of the live vaccine. Four groups (G) of cattle were each inoculated subcutaneously with 10 million Babesia bovis (vaccinal strain R1A), 10 million B. bigemina (vaccinal strain S1A) and 10 million Anaplasma centrale (strain M1). G1 and G2 consisted of ten Angus bulls 20-24 months old and ten Angus bulls 15-18 months old, respectively; G3 and G4 consisted of ten and 16 Holstein 1-month-old male calves, respectively. Blood samples were obtained on days 0, 10, 20, 30, 40, 50 and 60 after vaccination and the sera were analysed with an indirect immunofluorescent (IFA) test to detect antibodies to B. bovis (baseline dilution for a positive result 1:60) and B. bigemina (baseline dilution 1:120). Positive IFA titres were considered as evidence of the infectivity of the Babesia vaccinal strains contained in the vaccine. All Angus bulls were found positive to antibodies against both Babesia species, by day 20 (B. bovis) and day 30 (B. bigemina), whereas 10-25% of Holstein calves were negative throughout. The partial lack of vaccine infectivity in the calves was considered to be a consequence of innate resistance of young calves to Babesia. Antibody titres to B. bovis and B. bigemina declined by day 60 after vaccination. However, all cattle that were positive to B. bovis antibodies on day 50 were still positive to the IFA test 10 days later while 10%, 30% and 12% of cattle of G1, G2 and G3 that were positive to B. bigemina antibodies on day 50 after vaccination were found negative to the IFA test on day 60. In future, samples taken on days 40-50 will be used for detection of B. bigemina antibodies in vaccinated cattle, on day 60 for A. centrale and on either occasion for B. bovis. The reaction to the inoculation of B. bigemina S1A strain appears to lag behind the reaction to B. bovis R1A strain. It is not certain if this is a normal reaction to this B. bigemina strain or the result of interaction with the B. bovis strain.     

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.     

Prediction of microcirculatory oxygen transport by erythrocyte/hemoglobin solution mixtures

Vaccination with naked DNA may be an alternative to conventional vaccines because it combines the efficacy of attenuated vaccines with the biological safety of inactivated vaccines. We recently showed that the vaccination with naked DNA coding for the immunorelevant glycoprotein D (gD) of pseudorabies virus (PRV) induced both antibody and cell-mediated immunity in pigs and provided protection against challenge infection. To determine whether the efficacy of the naked DNA vaccination against PRV could be improved, we compared three sets of variables. First, the efficacy of the naked DNA vaccine coding only for the immunorelevant gD was compared with a cocktail vaccine containing additional plasmids coding for two other immunorelevant glycoproteins, gB and gC. Second, the intramuscular route of vaccination was compared with the intradermal route. Third, the commonly used needle method of inoculation was compared with the needleless Pigjet injector method. Five groups of five pigs were vaccinated three times at 4-weeks intervals and challenged with the virulent NIA-3 strain of PRV 6 weeks after the last vaccination. Results showed that although the cocktail vaccine induced stronger cell-mediated immune responses than the vaccine containing only gD plasmid, both vaccines protected pigs equally well against challenge infection. Intradermal inoculation with a needle induced significantly stronger antibody and cell-mediated immune responses and better protection against challenge infection than intramuscular inoculation. Our data show that the route of administering DNA vaccines in pigs is important for an optimal induction of protective immunity.     

Antibody response to whole-virus and split-virus influenza vaccines in successful ageing

The antibody response to influenza vaccination has been variably reported to be decreased in elderly individuals. To determine the effect of ageing alone on this antibody response, a group of carefully-screened healthy elderly subjects were compared with young adult controls. Antibody titres for several strains of influenza were measured before and after vaccination with whole-virus (WVV) and split-virus influenza vaccines (SVV) in two successive years. In general, the antibody response to WVV was greater than the response to SVV. Both groups showed a similar response to the H3N2 strain but the elderly group showed a lower response to the H1N1 and B strains of virus contained in the vaccine. Antibodies to older strains of influenza A but not B were stimulated by vaccination with SVV. In the elderly group, the response to older viral strains was relatively increased compared with newer strains. In contrast, the young control group had better antibody responses to the newer than to the older strains of influenza tested. Reductions in the antibody response to influenza vaccination may, therefore, be related to the phenomenon of original antigenic sin and the cohort effect of exposure to H1N1 during childhood in the elderly group studied. The increased immunogenicity of WVV must be considered in light of the current wide use of SVV in the elderly.     

Skeletal bone morphogenetic proteins suppress the expression of collagenase-3 by rat osteoblasts

The protective efficacy of several live, recombinant anthrax vaccines given in a single-dose regimen was assessed with Hartley guinea pigs. These live vaccines were created by transforming DeltaANR and DeltaSterne, two nonencapsulated, nontoxinogenic strains of Bacillus anthracis, with four different recombinant plasmids that express the anthrax protective antigen (PA) protein to various degrees. This enabled us to assess the effect of the chromosomal background of the strain, as well as the amount of PA produced, on protective efficacy. There were no significant strain-related effects on PA production in vitro, plasmid stability in vivo, survival of the immunizing strain in the host, or protective efficacy of the immunizing infection. The protective efficacy of the live, recombinant anthrax vaccine strains correlated with the anti-PA antibody titers they elicited in vivo and the level of PA they produced in vitro.     

Efficacy of intratracheal administration of Newcastle disease vaccine in day-old chicks

Groups of day-old chicks with varying levels of parental antibody were vaccinated against Newcastle disease (B1 strain) with a commercially available device which simultaneously debeaks the chick and emits a fine spray of vaccine into its trachea. Some groups were also vaccinated (B1 or Lasota strain) with a commercially available vaccine sprayer at 9 days, 14 days, or 9 and 25 days of age. Response to vaccine was evaluated once each week during the experimental period of approximately 8 weeks HI titers were determined and 10 chicks were challenged with the Texas GB strain of Newcastle disease virus. In chicks with low to moderate levels of maternal antibody a satisfactory antibody response was attained by vaccination at 1 day of age, and in most cases resistance to challenge was evident by 3 weeks of age. Intratracheal vaccination of chicks with extremely high levels of maternal antibody had a minimal antibody response. All groups of chicks spray vaccinated at 9, 14, or 9 and 25 days of age showed a marked increase in antibody titer regardless of whether they had been vaccinated at 1 day of age.     

The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children

BACKGROUND: Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old. METHODS: Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions. RESULTS: The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001). CONCLUSIONS: A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.     

Improved protection against Venezuelan equine encephalitis by genetic engineering of a recombinant vaccinia virus

An improved vaccine is needed against Venezuelan equine encephalitis (VEE) virus because the existing live attenuated vaccine, TC-83, causes a high incidence of adverse effects, and the Formalin-inactivated vaccine, C-84, does not protect against airborne infection. A recombinant vaccine had previously been constructed in which the VEE structural proteins were expressed by vaccinia virus. Although protection against subcutaneous challenge with VEE was achieved, the vaccine had limited efficacy against aerosolized virus. We made a similar construct (WR100) and compared its performance with that of a recombinant vaccinia virus which had been altered in two ways (WR103) in order to improve its performance as a vaccine: a synthetic promoter was inserted upstream of the VEE coding sequence to increase the amount of VEE proteins produced, and a single nucleotide in the E2 glycoprotein gene was altered to enhance immunogenicity. The WR103 virus expressed greater amounts of VEE proteins on the surface of infected cells than did WR100, and this difference was found to correspond to a 3.5-fold increase in VEE protein production. Sera from mice immunized with WR103 contained elevated levels of antibody to VEE, and enhanced protection against subcutaneous challenge with the pathogenic Trinidad donkey strain was achieved. This altered construct could form the basis for a better vaccine against VEE.     

Efficacy of a novel infectious bursal disease virus immune complex vaccine in broiler chickens

Two experiments were conducted to test the efficacy of a novel infectious bursal disease virus (IBDV) vaccine in broiler chickens with maternal IBDV immunity. The IBDV vaccine was formulated by mixing IBDV strain 2512 with bursal disease antibodies (BDA) to produce the IBDV-BDA complex vaccine. In Expt. I, 1-day-old Cobb x Cobb broiler chickens were vaccinated subcutaneously with either IBDV-BDA or commercial live intermediate IBDV vaccine (vaccine A) or were left unvaccinated. In Expt. 2, the vaccine A group was not included; instead, IBDV strain 2512 was included. Chickens were maintained in isolation houses. On day 28 (Expt. 1) and day 32 (Expt. 2) of age, chickens from each group were challenged with a standard USDA IBDV (STC strain) challenge. Challenged and unchallenged chickens were evaluated for their bursa/body weight ratios and antibody titers 3 days post-challenge. Bursae collected from Expt. 2 were examined histologically to evaluate bursal lesions and confirm gross examination. None of the unvaccinated chickens was protected against the challenge virus as evidenced by the presence of acute bursal lesions (edema/hemorrhage). All chickens receiving the IBDV-BDA complex or the IBDV strain 2512 (Expt. 2) were protected from the challenge virus as evidenced by no acute bursal lesions. Additionally, chickens receiving the IBDV-BDA complex vaccine or the IBDV strain 2512 had antibody titers to IBDV, indication the presence of an active immune response. In Expt. 1, chickens vaccinated with vaccine A and challenged had bursal lesions similar to those observed in the unvaccinated, challenged chickens. These chickens also showed no indication of active immunity against the virus. These results suggest that the 1-day-of-age-administered IBDV-BDA complex vaccine can induce active immunity and protection against a standard IBDV challenge in the face of variable levels of maternal IBDV immunity.     

Effect of levodopa therapy on visual evoked potentials and visual acuity in amblyopia

Between 10 and 11 years after children were vaccinated with Vi capsular polysaccharide of Salmonella typhi or meningococcal A + C control vaccine in a double blind randomized trial, we traced 83 subjects, aged 16-20 years. A blood sample was taken for determination of Vi antibody titres in both groups by radioimmunoassay. TO and TH titres were also done to assess if the participants had had recent exposure to typhoid fever. Fifty-eight percent of subjects in both groups had protective levels of Vi antibody against Salmonella typhi (a titre greater than 1 microgram ml-1). There was no significant difference in the levels of Vi antibodies in the cases versus the controls (p = 0.5). Two of the children who had received meningococcal A + C vaccine had recently had typhoid fever. Our data show that adolescents in typhoid endemic areas have high levels of Vi antibodies regardless of previous vaccination status, suggesting that Vi antibodies are acquired in adolescence by a large percentage of the population in this area. Moreover, Vi vaccination has led to ongoing antibody production in greater than 50% of Vi vaccinated children in an endemic area for a period of 10 years. Ongoing antigenic exposure may have contributed to these antibody levels.     

Immunobiology of bovine respiratory syncytial virus infections

This paper describes recent findings on the immunobiology of bovine respiratory syncytial virus (BRSV) infections. The pathobiology of alveolar macrophages and BRSV, and the immunological reaction of cattle to the virus after natural or experimental infection, or vaccination, were studied. Because in severe cases BRSV infection leads to lower respiratory tract disease, replication of BRSV in alveolar macrophages was studied. Alveolar macrophages, which are important aspecific defense cells in the lower respiratory tract, exhibited a high intrinsic resistance to BRSV. Furthermore, BRSV-infected alveolar macrophages produced significantly less nitric oxide (which has a bacteriocidal effect) than uninfected macrophages. The kinetics of antibody titres against the envelope protein G were different from those of antibody titres against the envelope protein F. For example, many animals that are reinfected do not possess antibodies against the G protein. After vaccination or after natural infection, antibody titres against the F and G protein, and against epitopes on the F protein, differed markedly, and also in animals with different MHC haplotypes. These findings may be related to differences in protection. The strains of BRSV that circulate in the Netherlands belong to the subgroups A and AB. There was no evidence for differences in virulence between these subgroups. BRSV could be detected in 30% of lungs obtained from calves suffering from severe lower respiratory tract disease. Based on cross-protection studies, calves that were infected with a virus from a particular BRSV subgroup were protected against reinfection with a virus from a different subgroup. A recombinant gE-protein negative bovine herpesvirus 1 vaccine carrying a gene encoding the G protein of BRSV, and a DNA vaccine encoding the same protein afforded protection after experimental challenge of calves. This offers the possibility to develop effective multivalent (gE-negative BHV1) marker vaccines in the future.     

Effect of dual-subtype vaccine against feline immunodeficiency virus infection

Dual-subtype feline immunodeficiency virus (FIV) vaccine, consisting of inactivated cells infected with subtypes A (Petaluma strain) and D (Shizuoka strain), was developed and tested for its vaccine efficacy against FIV infection in specific pathogen free (SPF) cats. Animals were monitored for proviral DNA by FIV-specific PCR and for FIV-specific antibody profiles by ELISA and virus-neutralization assays. In addition, blood from challenged cats was inoculated into naive SPF cats to confirm the viral status of the vaccinated cats. All cats immunized with Petaluma vaccine alone were protected against homologous Petaluma challenge, but only one of four cats was protected against heterologous Shizuoka challenge. More importantly, all cats immunized with the dual-subtype vaccine were protected against both Petaluma and Shizuoka challenges. These results suggest that a multi-subtype vaccine approach may provide the broad-spectrum immunity necessary for vaccine protection against strains from different subtypes.     

Seroconversion of a trivalent measles, mumps, and rubella vaccine in children aged 9 and 15 months

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.     

Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine

The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30-MDP and MDP-Lys(L18), on the ability of an inactivated vaccine of B-1 virus (B-1 vaccine) to induce immune response against Hantavirus causing hemorrhagic fever with renal syndrome (HFRS) was examined. When mice were immunized subcutaneously (s.c.) twice at 2-week intervals with B-1 vaccine admixed with or without 100 micrograms mouse-1 of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)], mice immunized with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed significantly higher indirect fluorescent antibody (IFA) titers against HFRS virus than mice immunized with B-1 vaccine alone. Both mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) also exhibited significantly higher neutralizing antibody titers against HFRS virus than mice immunized with B-1 vaccine alone during 3-9 weeks after the primary immunization. The evaluation of antibody-producing cells by enzyme-linked immunospot (ELISPOT) assay on week 4 revealed that both MDP derivatives enhanced the number of HFRS virus-specific IgG1 and IgM antibody-producing cells. Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed a higher level of Th-2 type cytokines, IL-4 and IL-6, in sera than mice treated with B-1 alone. In an in-vitro analysis of T lymphocyte proliferation to baculovirus-expressed recombinant nucleocapsid protein (rNP) of Hantaan 76-118 strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on week 4 showed a significantly higher proliferating activity than those treated with B-1 vaccine alone. In addition, when mice were immunized once with B-1 vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by intrafootpad (i.f.) injection of B-1 vaccine on day 7, mice immunized with B-1/B30-MDP and B-1/MDP-Lys(L18) induced a higher delayed-type hypersensitivity (DTH) reaction than mice immunized with B-1 vaccine alone. These results suggest that B30-MDP and MDP-Lys(L18) are useful immunoadjuvants to enhance the ability of inactivated B-1 vaccine to induce a humoral and cellular response to HFRS virus.     

Effects of Ca(2+)-channel drugs on K(+)-induced respiration in skeletal muscles

The immunogenicity and pathogenicity of a strain of respiratory syncytial (RS) virus modified by sequential induction of three temperature-sensitive (ts) mutations have been evaluated by intranasal administration to 22 adult volunteers. This modified virus, a triple ts mutant designated ts1C, was derived from a double mutant ts1B evaluated in a previous trial. The original isolate (strain RSS-2) and all its derivatives were propagated throughout in human diploid cells in a specially assigned laboratory. The triple mutant ts1C is unable to multiply in MRC-5 cells at 37 degrees C and above. Following nasal administration of ts1C, immune responses were observed in volunteers with low pre-existing neutralizing antibody titres. The ability of mutant ts1C to induce upper respiratory tract disease in adults was greatly diminished in comparison with the non-ts wild-type virus, but not markedly more so than a previously tested double ts mutant (ts1B) which replicates at 37 degrees C. Mutant ts1C, however, may have greater potential as a live vaccine in view of its inherently greater genetic stability.     

Induction of apoptosis in equine chorionic gonadotropin (eCG)-primed rat ovaries by anti-eCG antibody

BACKGROUND: Pneumococcal infections are a common cause of morbidity and mortality among elderly people. Protection against pneumococcal infections is mediated by serotype-specific antibodies to capsular polysaccharides. To obtain an estimate of anti-pneumococcal immunity, prevalence and levels of pneumococcal antibodies were studied in an unvaccinated elderly population. METHODS: IgG antibodies to pneumococcal serotypes 3, 6A, and B and to cell wall polysaccharide (C-PS, a common antigen to all pneumococci) were measured by enzyme immuno-assay in 480 subjects aged 64-97 years (206 men, 274 women) who were a random sample (41%) of elderly inhabitants in a semirural community in Finland. RESULTS: An average of 10% of the elderly lacked antibodies to serotypes 3, 6A, and 8, and 62% of the elderly had them in low titres only. Anti-C-PS antibodies were found in 99% of the elderly, and in significantly higher titres than anti-capsular antibodies. Antibody titres to C-PS and to type 6A decreased with age. Elderly women had significantly lower antibody levels than men. Among the men, current smokers had higher antibody titres than non-smokers; in the women, this analysis was not possible because of infrequent history of smoking. The effect of smoking on antibody titres was reversible after cessation of smoking. CONCLUSIONS: A considerable proportion of the elderly lacked protective antibodies to commonly infecting pneumococcal serotypes 3, 6A, and 8. Smoking increased the prevalence and levels of pneumococcal antibodies probably as a consequence of numerous respiratory infections. These observations emphasize the importance of administration of the pneumococcal vaccine among the elderly.