Immunotherapy for recurrent pregnancy loss

When immunomodulation is used on an unselected population with recurrent miscarriage (RM), there is no improvement in the live birth rate. However, when the population is selected for a poor prognosis, or immune phenomena, immunotherapy has been shown to be effective. This review discusses four immunomodulatory agents, namely, paternal leukocyte immunization, intravenous immunoglobulin (IVIg), intralipid, and filgrastim. The presence of embryonic aneuploidy may confound the results of treatment, therefore creating an impression of futility when treatment may be highly effective in saving pregnancies that can be saved. Additionally, in an unselected population with RM, there is a relatively good prognosis of 60–80% for a subsequent live birth depending on whether the definition of ≥2 or ≥3 miscarriages is used. Hence, spontaneous prognosis must be taken into account, which has not been the case in previous trials.This review discusses the possible immune-mediated mechanisms of pregnancy loss and the means whereby immunotherapy may modulate these mechanisms.     

Expression of the β‐adhesin part of HRgpA in Sprague Dawley rats induces a specific antibody response

The β‐adhesin part of the Porphyromonas gingivalis W50 (ATCC 53978) protease HRgpA was cloned in an eukaryotic expression vector and expressed in COS‐7 cells. The monoclonal antibody MAb (61BG1.3), specific for the hemagglutinating domain of β‐adhesin, recognized the expressed β‐adhesin in the transfected cells both by immunoblot and immunofluorescence. Sprague Dawley rats were immunized intramuscularly with β‐adhesin encoding expression plasmid and expression plasmid without β‐adhesin insert. Skeletal muscle tissue at the site of immunization in the β‐adhesin immunized animals was shown to express this protein. The immunization induced a β‐adhesin‐specific antibody response. Sera from the immunized animals were tested for hemagglutination inhibiting activity. Due to high natural inhibiting activity in all rat sera tested, no increased hemagglutination inhibition was detected in sera from the β‐adhesin immunized animals.     

中药提高AIDS患者免疫功能的研究

艾滋病在我国已进入快速传播期，积极开展中医药治疗艾滋病研究具有重要意义。中医学理论认为，艾滋病的病因不外“正虚”、“邪侵”两端。即邪毒入侵和精亏气虚；病机为脏腑虚损和气血津液失常；临床和实验研究已发现一批治疗艾滋病有效的中药，作用机理主要是抑制艾滋病病毒，调整免疫功能和控制机会性感染；其中以增强患者免疫功能最具有中医特色。     

Immunogenicity study of low-dose administration of hepatitis B virus vaccine in newborn infants: A cost reduction trial

Different doses of hepatitis B virus vaccine—prepared by Korea Green Cross Corporation, were given to healthy infants born to HBsAg-negative mothers at birth, 1 and 6 months of age. A dose of 2 μg was administered intradermally in Group A and, in the three other groups, the vaccine was given intramuscularly (i.m.). An adequate follow-up observation was possible for 9 months after birth in 22, 25, 23 and 21 infants in Groups A, B, C and D, respecvely.
Group C (5 μg, i.m.) produced seroconversion most rapidly, showing the highest rate (96%) at 9 months of age. The lowest seroconversion rate (5%) was found at the age of 1 month in Group A subjects, but the rate increased to 91% after a booster dose was given at 6 months of age.
While it can be concluded that a 5 μg i.m. dose of vaccine at 0, 1 and 6 months of age is optimum for the immunization of infants in efficacy and economy, a 2 μg intradermal dose can also be considered as an immunogenic and economical regimen, though the immune response is slower and a special technique is required for immunization.     

Synthesis of a new carrier for immunization: polytuftsin

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCI)-Thr-Lys-(2-CI-Z)-Pro in the presence of HOBt . Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10–26 and 39–55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA . Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCI 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.     

Comparison of class and subclass antibody response to live and UV-inactivated RSV administered intranasally in mice.

To determine the effect of viral dose and replication on the subclass antibody response to RSV, mice were immunized intranasally with different doses of live RSV (10(4)-10(6) pfu) and compared to mice given an immunizing regimen of UV-inactivated RSV. Mice given the 10(6) pfu dose of live RSV and mice given the 40 micrograms dose of UV-inactivated RSV had comparable class specific antibody responses to whole RSV in serum and respiratory secretions. Serum from these two groups of mice were then compared for IgG subclass response to whole RSV. A predominance of IgG2a subclass antibody was found for both immunizing regimens, and no significant differences in subclass proportions were noted between regimens. These two regimens were then compared for serum total IgG response to RSV surface glycoproteins F and G. The serum IgG response to these glycoproteins was lower after immunization with UV-inactivated RSV than after live-RSV immunization (F: P = 0.03; G: P less than 0.05), even though the serum IgG response of the two groups to whole RSV was comparable. The IgG subclass response to surface glycoproteins was evaluated for live RSV immunization. The proportions of subclass antibody responses to glycoprotein F were comparable to the subclass response proportions to whole RSV and were not characteristic of a T-dependent response pattern. The subclass profile for glycoprotein G was not comparable to that of whole RSV but was suggestive of a T-independent response pattern.     

Antibody-dependent neutrophil-mediated parasite killing in non-lethal rodent malaria

The effects of administrating recombinant human granulocyte colony-stimulating factor (rhG-CSF) and passively transferring immune serum on infection with an attenuated variant of Plasmodium berghei XAT (Pb XAT), in severe combined immunodeficiency (SCID) mice were examined. In immune competent (C.B-17) mice, the attenuated parasite infection was inevitably self-resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas SCID mice were unable to control parasite growth and all the mice died. Continuous administration with rhG-CSF caused neutrophilic granulocytosis in both SCID and C.B-17 mice. The effect of rhG-CSF on the infection in C.B-17 mice was to suppress the course of the parasitaemia at an early phase whereas it had no effect in SCID mice. When immune serum was transferred on the day of infection, the prepatent period was prolonged two days in both SCID and C.B-17 mice. When administration with rhG-CSF was combined with transfer of immune serum, SCID mice showed four days delay in patency and degenerating parasites were seen during the course of parasitaemia, although the infection was ultimately fatal. C.B-17 mice similarly treated showed a seven day delay in the onset of the patent parasitaemia which was of a lesser magnitude and shorter in duration compared with control mice. On the other hand, when C.B-17 mice were splenectomized three weeks before infection and then treated with rhG-CSF and immune serum, no degenerating parasites were seen during the infection and all mice died with high parasitaemias. These results show that antibody-dependent neutrophil-mediated parasite killing may occur in the spleen of mice infected with P. berghei XAT.     

Familial and socioeconomic influences on children''s well-being: An examination of preschool children in Kenya

As patterns of family formation change, it is important to know how children's lives are affected by their parents' marital and socioeconomic circumstances. Using data from the 1993 Kenya Demographic and Health Survey, this study shows that children of never married and formerly married mothers have significantly higher probabilities of polio dropout and acute undernutrition than those of monogamously married mothers. The number of male household members of working age greatly enhances the chances of full immunization and the nutritional status of children whose mothers were previously married. For children of never married mothers, the benefits of residing with males of working age are largely a function of ethnicity. The results also show that, although children are not disadvantaged nutritionally when their fathers have more than one wife, polygyny is associated with a higher probability of polio dropout and lower probability of full immunization than monogamy. Higher socioeconomic status is associated with a greater probability of full immunization and a lower probability of malnutrition but socioeconomic factors do not explain the effects of mothers' marital status. The findings underscore the complex realities of family interaction and the importance of the broader social context in accounting for variations in child welfare across diverse marital situations.     

Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi chabaudi in CBA/Ca mice. III. Protective and suppressive responses induced by immunization with purified antigens

The protective effect of affinity purified antigen has been investigated in an experimental model for malaria which shows a well marked recrudescence of parasitaemia, a feature of the disease in man. A monoclonal antibody (MoAb) recognizing an epitope common to two genetically distinct cloned lines of Plasmodium chabaudi (AS and CB), was used to purify a Mr250,000 polymorphic schizont antigen (PSA) from these parasites. The purified preparations were then examined for the presence of specific and cross-reactive epitopes by immunoprecipitation with a panel of MoAb raised against P. chabaudi AS. When tested previously on smears of parasitized blood by immunofluorescence, or against lysates of parasitized erythrocytes by immunoprecipitation, most of these MoAb had been found to be AS specific. When either AS or CB affinity purified Mr250,000 PSA was used as the target, these same MoAb immunoprecipitated both antigens, and in some cases, a number of associated polypeptides (AP) which copurify with the Mr250,000 PSA. Subsequently, mice were immunized with either the purified AS or CB antigens in Freund's complete adjuvant (FCA). Prechallenge sera were compared by indirect immunofluorescence and immunoprecipitation. Sera from mice immunized with AS antigen reacted strongly with AS and cross-reacted with CB parasite preparations. Pre-challenge serum from CB antigen immunized mice reacted well with CB, but only faintly with AS preparations. In mice immunized with the AS antigen and then challenged with either AS or CB parasites, the initial parasitaemias were delayed in appearance and the height of the peak parasitaemia reduced, an effect which was most pronounced after challenge with homologous parasites. Only homologous challenge of the mice immunized with CB antigen produced statistically significant modification of the initial parasitaemia. In the immunized mice challenged with homologous parasites, the delayed appearance and slightly reduced peak of the primary parasitaemia was associated with delayed resolution of the patent parasitaemia and significant enhancement of the recrudescence.     

Vaccination against the cat flea Ctenocephalides felis felis

Non-chemical control of haematophagous parasites is a desirable goal. We report here on the use of concealed antigens from the major digestive organ of the cat-flea as vaccine components. Rabbits were immunized with various antigens from cat flea midguts, and immunoglobulin from these rabbits was fed to cat fleas in an artifical feeding system. Antibody produced against soluble antigens from the midguts of fed fleas was able to kill fleas in this system. Dogs were then immunized with various antigen preparations, and challenged for a week with live fleas. Significantly fewer live fleas were recovered from dogs immunized with fed midgut supernatant, and recovered live female fleas produced significantly fewer eggs. This study indicates the possibility of vaccination as a means of control of flea, and possibly other blood sucking insect populations.