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Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys.

Infection of macaques with simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) are useful models for studies of immunotherapy and vaccination against HIV as well as for testing of antiviral drugs. Vaccine research showing protective immunity in immunized monkeys has indicated that it will be possible to develop a vaccine for prevention of human HIV infection, although many hurdles remain. The design of an HIV vaccine would be helped if the basis of the protective immunity could be elucidated. Passive immune prophylaxis offers a means to determine the relative role of antibodies in protection against infection. We have studied whether a transfer of antibodies can prevent HIV-2 and SIVsm (SIV of sooty mangabey origin) infection in cynomolgus monkeys. Sera with high antibody titres were collected, heat-treated and injected into naive animals 6 h before challenge with 10-100 monkey-infectious doses of live homologous virus. All control animals treated with normal monkey serum (n = 6) or no serum (n = 39) became infected by the challenge virus, whereas five out of seven animals pretreated with antibody-containing serum at a dose of 9 ml kg-1 resisted infection. Thus passively transferred antibodies can protect against a low-dose lentivirus challenge in a nonhuman primate.

Animals↗

[Passive immunization against rabies (author's transl)].

Passive immunization has proven an important complementary method for protection of an infected organism against rabies in the very first phase after virus contact. Passive-active immunization is by far superior compared to vaccination only. A few cases of human rabies after serovaccination in due time might be due to interference (immunosuppression) of active antibody formation after vaccination by passiively administered performed heterologous rabies immune globulin. This "interference phenomenon" can probably be explained as an imbalance of antigen and antibody in vivo, i.e. antigen masking and, hence, blocking of the immune reaction on its afferent branch. Both, 19S- and 7S- antibody moleculars, are able to induce interference. Whereas the old heterologous antisera from horse or mule, in an extremely high percentage, provoked moderate or severe side effects of such as urticaria, serum sickness, immune complex nephritis etc., the now available homologous Rabies Immune Globulin of Human Origin (RIGH) is very well tolerated, of long-lasting effectiveness and does not interfere with active antibody formation after application of HDCS-tissues culture vaccine, when an amount of 20 I.U./kg bodyweight of RIGH and 6 diseases of HDCS-vaccine on days, 0, 3, 7, 14, 30 and 90 (Essen schedule postexposure vaccination) is used.

Humans↗

Passive immunity in transmissible gastroenteritis of swine: immunoglobulin characteristics of antibodies in milk after inoculating virus by different routes.

Pregnant swine were exposed to transmissible gastroenteritis (TGE) virus by different routes, and their serum, colostrum, and mild were examined for titer and immunoglobulin (Ig) class of antibodies. When 2 to 4 days old, the litters of most of these animals were challenged with virulent TGE virus to determine the effectiveness of passive immunity. After two oral/intranasal exposures to attenuated virus, none of the six pregnant animals became sick. TGE antibodies in milk were primarily or solely of the IgG class, although low levels of IgA antibodies were detected in three animals. Pigs in the five challenged litters received some passive immunity, the mortality being 25%. After intramuscular injection of six pregnant swine with virulent virus, two types of clinical and immunological responses were observed, presumably dependent on whether the gut was infected by an hematogenous spread of the virus. Three became sick, showing typical clinical signs of TGE, and their immunological response was characterized by the occurrence in milk of antibodies of the IgA class. A good degree (0% mortality) of passive immunity occurred upon challenge of the suckling pigs. In contrast, in three pregnant animals that did not sicken, antibody in milk was primarily of the IgG calss, and poor (69% mortality) passive immunity occurred. After intramammary injections of three pregnant swine with virulent virus, no sickness was observed and the immunological response was characterized by the occurrence in colostrum of high titers of TGE antibodies that were primarily or solely of the IgG class; good (0% mortality) passive immunity occured. The occurrence in milk of TGE antibodies of the IgA class was associated with an intestinal infection, whereas antibodies of the IgG class resulted from a parenteral antigenic stimulation. The role of antigenic stimulation of the intestinal tract for providing antibodies in milk of the IgA class is discussed. Passive immunity against intestinal infection with TGE virus was generally more complete in pigs ingesting antibodies of the IgA than of the IgG class.

Absorption↗

Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans.

Local passive immunization with monoclonal antibodies (MAbs) raised against streptococcal antigen (SA) I/II protects monkeys against colonization of teeth by Streptococcus mutans and the subsequent development of dental caries. In this study we extended the preclinical experiments to human subjects. In the first study of eight healthy subjects, four had anti-SA I/II MAb (immunoglobulin G2a [IgG2a]) and four had saline applied to their teeth on three occasions. A streptomycin-resistant S. mutans strain (Guy K2 strain, serotype c) was then implanted onto the teeth, and the organism was cultured sequentially from dental plaque and saliva up to 100 days after the first treatment with MAb. Decreased colonization by S. mutans was found in the dental plaque collected from smooth surfaces and fissures and in saliva of subjects whose teeth were treated with the MAb, as compared with the saline-treated control subjects. The experiment was then repeated on seven new subjects, and the effect of anti-SA I/II MAb was compared with that of an unrelated MAb to Campylobacter jejuni. The results again showed a consistently lower level of colonization of teeth in the anti-SA I/II MAb-treated subjects as compared with those sham immunized with the unrelated MAb. There was little difference in serum IgG, IgM, or IgA, gingival fluid IgG, or salivary IgA anti-SA I/II antibodies between the immunized and sham-immunized subjects, before and after the investigation. No side effects were observed, and the gingival and plaque indices remained unchanged. A sensitive radioimmunoassay failed to detect changes in anti-MAb (IgG2a) antibodies in any of the three fluids examined. We suggest that local passive immunization by means of MAb might be an alternative approach in the prevention of colonization of teeth by S. mutans and the development of dental caries.

Adult↗

Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice.

Phosphorylcholine (PC) headgroup is one of the neoantigens exposed by LDL oxidation that can elicit an immune response. Active immunization with Streptococcus pneumoniae, which bears PC on its cell wall, reduced atherosclerosis in hypercholesterolemic mice and this effect was attributed to an immune response to PC. In this study we tested the hypothesis that passive immunization with a monoclonal anti-PC IgM antibody can be athero-protective in a murine model of native aortic and vein graft atherosclerosis. Inferior vena cava from 16-week-old donor male apoE-null mice was grafted into right carotid artery of age-matched male recipient apoE-null mice. Anti-PC IgM titers were evaluated before and 4 weeks after surgery. For the immunization protocol, a separate group of mice received weekly intraperitoneal injection of monoclonal anti-PC IgM (400 microg) for 4 weeks, starting the day of surgery. Controls received PBS or pooled polyclonal IgM. Anti-PC IgM titres significantly increased at 4 weeks following surgery. Passive immunization with anti-PC IgM reduced vein graft plaque size and neointimal thickness resulting in a larger luminal area; in addition immunization reduced the inflammatory cell content of the plaques. There was no significant effect on the established native aortic atherosclerotic lesions. Immunization did not affect circulating cholesterol levels. Taken together our data suggest that passive immunization with anti-PC IgM significantly reduces vein graft lesion size with less inflammatory phenotype without affecting cholesterol levels, indicating an athero-protective immune response to PC. Lack of effect on established native aortic lesions may have been due to short duration of therapy and/or reduced efficacy in established lesions as compared to evolving lesions of vein graft atherosclerosis.

Animals↗

Active and passive immunization strategies for Pseudomonas aeruginosa pneumonia.

The unusually high mortality associated with Pseudomonas aeruginosa pneumonia has provided an incentive for the development of immunologic strategies for preventing or treating this infection. A guinea pig model of experimental P. aeruginosa pneumonia was employed to determine prophylactic efficacy of active immunization with a detoxified lipopolysaccharide vaccine; efficacy of passive immune therapy utilizing a new hyperimmune immunoglobulin G preparation enriched for antibodies to P. aeruginosa immunotypes 1, 2, 4, and 6; and efficacy of active and passive immunization against the mucoid exopolysaccharide antigen associated with mucoid strains of P. aeruginosa. Each of these immunologic methods provided an element of protection against P. aeruginosa pneumonia.

Animals↗

Pulmonary clearance and lesions of lung and air sac in passively immunized and unimmunized turkeys following exposure to aerosolized Escherichia coli.

Two groups of young turkeys, one passively immunized with homologous hyperimmune serum and the other unimmunized but receiving normal turkey serum, were aerosolized with Escherichia coli. Clearance of bacteria from lung and gross and microscopic lung and air-sac lesions were determined after necropsy at timed intervals. The group mean bacterial count in lungs of passively immunized turkeys was significantly less than the mean count in unimmunized turkeys. Lung lesions were generally similar in both groups and were focused in lymphoid nodules, at the junction of primary and secondary bronchi, and at the ostia to the air sacs. Unimmunized birds developed grossly evident purulent airsacculitis by 72 hours after aerosol exposure, whereas passively immunized birds did not.

Air Sacs↗

Xenograft rejection of fetal porcine islet-like cell clusters in the rat: effects of active and passive immunization.

The process of islet xenograft rejection is still poorly understood. To elucidate further possible mechanism(s) involved in xenograft rejection, the effect of different immunization protocols was investigated. Fetal porcine islet-like cell clusters (ICCs) were transplanted under the kidney capsule in otherwise untreated rats, rats pre-immunized by s.c. injections of ICCs and in rats passively immunized with immune serum. The rejection process was evaluated with regard to antibody and complement deposition in the graft, as well as to morphology and phenotype of the infiltrating cells. In otherwise untreated animals, a moderate perigraft mononuclear cell infiltrate was seen after 3 days. Graft destruction became evident on day 6 with marked intragraft infiltration by macrophages (ED1 positive), whereas T cells were in the minority and mainly located in the perigraft area. In contrast to the findings in non-immunized rats, the rejection process in pre-immunized rats was characterized by marked intragraft infiltration by macrophages 3 days after transplantation. Moreover, both T cells and macrophages heavily infiltrated the adjacent kidney parenchyma, and major histocompatibility complex (MHC) class II expression in surrounding kidney tubular cells was concomitantly enhanced. Syngeneic rat islets mixed with porcine ICCs escaped the rejection process in non-immunized rats but were affected in pre-immunized animals. Thus, the specificity of the rejection process in non-immunized animals seems to be lost in pre-immunized animals. The early macrophage infiltration was also accelerated in rats passively immunized with immune serum, but no early switch from perigraft to intragraft infiltration or subsequent cellular infiltration in the adjacent kidney parenchyma was seen. Circulating xenoreactive antibodies of the IgG isotype increased after transplantation in normal and otherwise untreated rats. No distinct IgG deposition in the ICC xenografts was observed until day 12 after transplantation in untreated rats, whereas perigraft deposition of IgG was found 1 day after transplantation in pre-immunized rats and in rats given immune serum. No deposition of complement was observed within the ICC xenograft in any of the groups during the observation period. The dependence on T cells, the massive infiltration of macrophages with a unique phenotype, the cellular distribution, and the loss of specificity (bystander killing) of the rejection process in immunized rats suggest that ICC xenograft rejection shares some of its main characteristics with a delayed type hypersensitivity-like (DTH) immune response.

Animals↗

Effect of vaccinal and passive immunity on experimental infection of pigs with porcine parvovirus.

One group of 5 pigs was vaccinated twice at 6 and 8 weeks of age with an inactivated porcine parvovirus (PPV) vaccine. A 2nd group of 5 pigs was passively immunized at 9 weeks of age, and a 3rd group of 5 pigs served as nonimmunized controls. The immunity of all pigs was challenged with live PPV at 10 weeks of age. Four vaccinated pigs with hemagglutinating-inhibiting (HI) antibody titer of 160 to 640 and 3 passively immunized pigs with HI titer of 80 to 160 were resistant to PPV infection. Neither infective virus nor viral antigen was detected in their tissues. However, virus replicated in tissues of 1 vaccinated and 2 passively immunized pigs with HI titers of 80, and viral antigen was detected in their lymphoid tissues. There was a 4-fold increase of HI titer in 1 passively immunized pig. Viremia and viral excretion were not detected in any of the vaccinated or passively immunized pigs. In contrast, PPV replicated in the tissues of nonimmunized pigs; both virus and viral antigen were detected in their tissues, and they produced HI antibodies to PPV. All nonimmunized pigs developed viremia and shed virus in oral secretions and feces. Our data show that a high level of humoral antibodies is required for protection from PPV infection.

Animals↗

Passive immunization against cytomegalovirus in allograft recipients. The Rotterdam Heart Transplant Program experience.

We analyzed the results of passive immunization against CMV in 146 heart transplant recipients. The 65 seronegative recipients were prophylactically treated with anti-CMV immunoglobulins during and after the operation. Twenty-nine of these 65 patients received a seropositive donor heart. CMV infection occurred in 21/65 seronegative and in 40/81 seropositive recipients (difference not significant). The incidence of CMV infection in seronegative recipients of a CMV-matched donor heart (3/34) was significantly lower than in seronegative recipients of a positive donor heart and lower than in seropositive recipients, but no significant difference in infection rate was found between the two latter groups (18/29 vs. 40/81). Although primary infection more frequently resulted in CMV disease than secondary infection (11/21 vs. 10/40) no difference in incidence of disease was noted between seronegative and seropositive patients (11/65 vs. 10/81), nor was there a difference in the severity of symptoms following primary or secondary infection. There was a higher incidence of CMV disease in all patients who received a heart from a seropositive donor versus a seronegative donor. However, after transplantation of a heart from a seropositive donor the incidence (27%) of CMV disease observed in our passively immunized seronegative patients was the same as in the patients with naturally acquired seropositivity. There was no difference in the prevalence of coronary artery disease between patients with and without CMV infection or disease. We conclude that using the current passive immunization scheme the occurrence of CMV infection and disease is largely dependent on the serostatus of the donor.

Adolescent↗

Prophylaxis of Pseudomonas aeruginosa infections in leukopenic mice by a combination of active and passive immunization.

Mice rendered leukopenic with cyclophosphamide and then challenged with viable Pseudomonas aeruginosa were used to determine the protective efficacy of active immunization against exotoxin A and of passive immunization with human antiserum to Escherichia coli J5, a rough mutant of Escherichia coli O111:B4. Neither treatment alone provided a greater degree of protection than its respective control. However, the combination of these treatments produced a moderate, yet consistent, increase in the survival of infected immunosuppressed mice.

ADP Ribose Transferases↗

Passive immunization against nicotine attenuates nicotine discrimination.

Ten rats were trained in a two lever operant chamber to press different levers after a nicotine injection (0.14 mg/kg s.c.) or a saline injection on an FR10 schedule. The rats were then injected i.p. with either 150 mg nicotine-specific IgG or the same amount of control IgG from non-immunized rabbits. On successive days, they were retested with both levers active after a saline injection, a full training dose of nicotine and a half dose of nicotine (0.07 mg/kg s.c.). After saline injection, both groups pressed the saline lever almost exclusively. After each of the nicotine doses, the immunized rats performed a significantly lower percentage of their lever presses on the nicotine lever than did non-immunized rats. The results suggest that passive immunization can interfere with the stimulus properties of nicotine.

Animals↗

Prevention of cytomegalovirus infection after organ transplantation with passive immunization. An analysis of 6 randomized clinical trials.

We performed a meta-analysis of 6 randomized clinical trials to study the efficacy of passive immunization against CMV in solid organ transplantation. The results indicate that passive immunization against CMV prevents (fatal) CMV disease in CMV seronegative recipients of a CMV seropositive allograft, even when treated with additional immunosuppression in case of rejections. Passive immunization with anti-CMV immunoglobulin preparations did not reduce the incidence of CMV infection or disease in CMV seropositive recipients.

Cytomegalovirus Infections↗

Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental caries.

Local passive immunization with monoclonal antibodies (Mc Ab) to Streptococcus mutans was attempted as an alternative approach to active systemic immunization. We prepared an immunoglobulin G class Mc Ab to the cell surface protein determinant of streptococcal antigen I/II and applied it repeatedly to the teeth of rhesus monkeys. This resulted in decreased colonization by S. mutans in fissures and smooth surfaces of teeth and no dental caries, unlike the results in control animals, which developed caries and showed a high proportion of S. mutans on their teeth. There was no significant difference in serum, salivary, or gingival fluid antibodies to S. mutans between the two groups of animals. Any objections raised over systemic immunization inducing cross-reactive antibodies are therefore overcome by local passive immunization. The mechanism of prevention of colonization has not been established, but we postulate that the Mc Ab which is directed against an important cell surface antigenic determinant of S. mutans (streptococcal antigen I/II) prevents adherence of S. mutans to the acquired pellicle on the tooth surface. S. mutans reacts with the Mc Ab and becomes opsonized, phagocytosed, and killed by the local gingival traffic of neutrophils.

Animals↗

Efficacy of intravenous plasma to transfer passive immunity in clinically healthy and clinically ill equine neonates with failure of passive transfer.

The efficacy intravenous plasma to transfer passive immunity to clinically healthy colostrum-deprived and clinically ill foals with failure of passive transfer was investigated. Efficacy of transfer was evaluated by the elevation of serum IgG per gram of IgG administered as a function of body weight. Colostrum deprived healthy foals had a significantly greater increase in serum IgG than did clinically ill foals with failure of passive transfer. Knowledge of the IgG content of plasma to be administered and the health status of a foal with failure of passive transfer should allow more accurate prediction of an individual foal's response to treatment.

Animals↗

An investigation into the mechanism of protection by local passive immunization with monoclonal antibodies against Streptococcus mutans.

Local oral passive immunization with Streptococcus mutans-specific monoclonal antibody (MAb) (Guy's 13) prevented recolonization by indigenous S. mutans in human volunteers who had first been treated with a conventional antibacterial agent (chlorhexidine). The F(ab')2 fragment of the MAb was as protective as the intact immunoglobulin G, but the Fab fragment of the molecule failed to prevent recolonization of S. mutans. In subjects receiving the MAb Fab fragment, S. mutans levels in dental plaque and saliva reappeared at a similar rate to that found in sham-immunized subjects who received either saline or a nonprotective MAb. In vitro, MAb had no bacteriostatic or bacteriocidal effect on S. mutans. However, S. mutans grown in the presence of either intact immunoglobulin G MAb or the F(ab')2 fragment formed very long chains, which resulted in clumping of the cells. S. mutans grown with either saline or the MAb Fab fragment formed significantly shorter chains, more characteristic of streptococcal growth in liquid media. The results suggest that the two binding sites of the MAb molecule may be an essential feature for preventing streptococcal colonization but that the ability to bind to phagocytes and activate complement which resides in the Fc fragment is not essential. Protection against colonization by S. mutans lasting up to 2 years was observed in immunized subjects, although MAb was applied over a period of only 3 weeks. Furthermore, functional MAb was detected up to 3 days following application of MAb to the teeth. The long-term protection could not be accounted for by a persistence of MAb on the tooth surface, and we have suggested that it may be due to a shift in the balance of the oral flora which discouraged recolonization by S. mutans. However, examination of the proportions of Streptococcus sanguis and veillonella species in the recolonization experiments failed to reveal a significant change in the proportions of either organism, which returned to approximately the preexperimental levels in both the immunized and control groups. These findings confirm the in vivo functional specificity of the MAb to S. mutans but are not consistent with the suggestion that S. sanguis or veillonella take over the niche vacated by S. mutans, unless the shift in the proportion of these organisms cannot be detected by the method used.

Adult↗

Mouse sperm antigens that participate in fertilization. III. Passive immunization with a single monoclonal antisperm antibody inhibits pregnancy and fertilization in vivo.

Passive immunization was used to study the effect of antimouse sperm monoclonal antibodies on fertilization in vivo. The effects of two antibodies were compared in this investigation. One of them, M29, has been shown previously to localize to the equatorial segment of the sperm head and to inhibit mouse fertilization in vitro in a concentration-dependent manner. The second antibody, M2, binds to the same area of the sperm head, and also belongs to the M immunoglobulin class (IgM), but does not affect fertilization in vitro. Superovulated female mice received two antibody injections intraperitoneally (at the times of the pregnant mare's serum gonadotropin and human chorionic gonadotropin injections) at concentrations of 0.5-4.0 mg of IgM or control IgG; animals were mated within 6-12 h of the hCG injection. Fertilization and concomitant establishment of pregnancy were reduced significantly, in a dose-dependent manner, only in those animals immunized with M29 IgM (e.g., 4 mg M29 IgM: 12.6% of 304 eggs fertilized; 4 mg M2 IgM: 96% of 192 eggs fertilized). Intraperitoneal administration of the antibodies did not depress superovulation levels nor oocyte viability. 125I-labeled M29 IgM was used to determine the amount of antibody present in the oviductal ampulla at the time of fertilization in passively immunized mice. Luminal M29 IgM was found to be a linear function of the intraperitoneal dose: 0.002-0.003% of the injected dose was present in the oviductal lumen 14-16 h post-hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Passive immunization of the pig against gonadotropin releasing hormone during the follicular phase of the estrous cycle.

Three experiments were conducted to determine the effects of passively immunizing pigs against gonadotropin releasing hormone (GnRH) during the follicular phase of the estrous cycle. In Experiment 1, sows were given GnRH antibodies at weaning and they lacked estrogen secretion during the five days immediately after weaning and had delayed returns to estrus. In Experiment 2, gilts passively immunized against GnRH on Day 16 or 17 of the estrous cycle (Day 0 = first day of estrus) had lower (P<0.03) concentrations of estradiol-17beta than control gilts, and they did not exhibited estrus at the expected time (Days 18 to 22). When observed three weeks after passive immunization, control gilts had corpora lutea present on their ovaries, whereas GnRH-immunized gilts had follicles and no corpora lutea. The amount of GnRH antiserum given did not alter (P<0.05) serum concentrations of LH or pulsatile release of LH in sows and gilts. In Experiment 3, prepuberal gilts were given 1,000 IU PMSG at 0 h and GnRH antiserum at 72 and 120 h. This treatment lowered the preovulatory surge of LH and FSH, but it did not alter serum estradiol-17beta concentrations, the proportion of pigs exhibiting estrus, or the ovulation rate. These results indicate that passive immunization of pigs against GnRH before initiation of or during the early part of the follicular phase of the estrous cycle retards follicular development, whereas administration of GnRH antibodies during the latter stages of follicular development does not have an affect. Since the concentration of antibodies was not high enough to alter basal or pulsatile LH secretion, the mechanism of action of the GnRH antiserum may involve a direct ovarian action.

Journal Article↗