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Genetic control of immunity to Nematospiroides dubius: a 9-day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice.

Experiments were designed to re-examine the variables which influence the ability of single primary infections to elicit acquired immunity to Nematospiroides dubius, in particular the importance of the presence or absence of adult worms, as these are known to exert immunomodulatory effects. Briefly, anthelmintic abbreviated infections were considerably more effective at eliciting acquired immunity than longer infections in which adult worms were allowed to reside in the intestine. A 9-day anthelmintic abbreviated infection was extremely effective at stimulation of acquired immunity in NIH mice and very few immunising infection larvae were required. Immunity to subsequent reinfection developed rapidly after the primary infection worms had been eliminated; by day 21 post-infection, the mice were almost totally immune. Abbreviated infections were used to examine the capacity of a number of mouse strains to develop immunity to reinfection. Strains of mice were chosen to allow the effects of MHC linked and non-MHC linked (background) genes to be identified. CBA and C3H strains (both H-2k) were found to be weak responders to N. dubius. B10G (H-2q) mice responded better than C57Bl/10 (H-2b), although these strains have identical background genes. DBA/2 mice were stronger responders compared to BALB/c mice, both strains sharing a common MHC haplotype (H-2d). (NIH X B10G) F1 mice (H-2q) were better responders than either of the parental strains. Several mouse strains all sharing the H-2q haplotype were particularly effective at developing immunity to N. dubius, as were also SJL mice which were the sole representatives of the H-2s haplotype, in the present study. The results established that the response phenotype is influenced by both background and MHC genes and demonstrated gene complementation in the capacity of mice to acquire immunity to N. dubius.

Animals↗

Inability of spleen cells from chancre-immune rabbits to confer immunity to challenge with Treponema pallidum.

Although several lines of evidence suggest that cellular immune mechanisms play a role in controlling infection due to Treponema pallidum, recent studies have shown that induction of acquired cellular resistance by antigenically unrelated organisms fails to protect rabbits against syphilitic infection, thereby casting doubt on this hypothesis. In the present paper we describe attempts to transfer immunity to syphilis by using spleen cells from chancre-immune rabbits. Intravenous infusion of 2 X 10(8) spleen lymphocytes was capable of transferring acquired cellular resistance to Listeria and delayed hypersensitivity to tuberculin. However, in eight separate experiments using outbred or inbred rabbits, 2 X 10(8) spleen cells from syphilis-immune animals failed to confer resistance to T. pallidum whether by intravenous or intradermal challenge. Mixing immune lymphocytes with treponemes immediately before intradermal inoculation also failed to confer resistance. Despite the fact that syphilitic infection stimulates cellular immune mechanisms and induces acquired cellular resistance to antigenically unrelated organisms, cellular immunity may not play an important role in immunity to syphilis.

Animals↗

Protective immunity and delayed-type hypersensitivity in C57BL mice after immunization with live Mycobacterium lepraemurium and sonicated bacilli.

The immunizing effects of live Mycobacterium lepraemurium (MLM) and bacillary sonic extract (MLMSon) were compared in C57BL mice. MLMSon-immunized mice developed a delayed-type hypersensitivity (DTH) reaction when tested in the footpad with diluted MLMSon. The ability to develop a DTH reaction was transferable with immune cells but not with serum. Footpad testing with live MLM and MLMSon indicated that the specificity of the DTH response induced by MLMSon was different from that induced by infection with live bacilli. Two weeks after footpad inoculation with live MLM, MLMSon-immunized mice developed a strong local reaction to the bacilli. No local reaction developed in these mice after injection of the same number of heat-killed MLM. Studies of bacillary growth after inoculation with live MLM indicated that the bacilli did not multiply in micr previously inoculated with live MLM, but that they multiplied for about 2 weeks in LMLSon-immunized mice versus 4 weeks in the controls. The results suggest that immunization with MLMSon does not by itself induce a protective immune response, but creates a state in which the development of protective immunity is accelerated.

Animals↗

Protective immunity to Brucella ovis in BALB/c mice following recovery from primary infection or immunization with subcellular vaccines.

Experiments were performed with BALB/c mice to elucidate the roles of humoral and cell-mediated immune responses in the acquisition of protective immunity to Brucella ovis and to compare infection immunity with immunity developed through vaccination with a hot saline extract (HS) of B. ovis. Mice convalescing from a primary infection with B. ovis displayed a high level of resistance to reinfection, as evidenced by splenic bacterial counts decreased over 10,000-fold from control groups at 2 weeks after challenge. Passive transfer assays revealed that protection was mediated by both T lymphocytes and antibodies but that antibodies had a substantially greater role on the basis of log units of protection that were transferred. Antibodies specific for HS proteins in sera from convalescent mice were predominantly of the immunoglobulin G 2a and 3 isotypes. Vaccination with HS conferred good protection against B. ovis, but protection was greatly enhanced by the incorporation of QS-21 or other adjuvants. Protection provided by the HS vaccine resulted largely from immune responses to its protein moieties. A critical evaluation of the protective efficacy of the rough lipopolysaccharide component of HS was precluded by its poor immunogenicity in BALB/c mice. HS-QS-21 afforded protection against challenge infection with B. ovis as good as that which developed after a primary infection and as good as or better than that provided by attenuated Brucella melitensis vaccine strain Rev 1. Passive transfer experiments confirmed that the magnitudes of both humoral and cell-mediated forms of protective immunity were equivalent in mice vaccinated with HS-QS-21 and those recovering from a primary infection. Protective immunity to B. ovis in mice therefore resembled that to Brucella abortus, except that the relative roles of humoral and cell-mediated immunity, rather than being equivalent, were shifted toward a greater role for antibodies.

Animals↗

Induction of protective immunity against Japanese encephalitis in mice by immunization with a plasmid encoding Japanese encephalitis virus premembrane and envelope genes.

A DNA vaccine plasmid containing the Japanese encephalitis (JE) virus premembrane (prM) and envelope (E) genes (designated pcDNA3JEME) was evaluated for immunogenicity and protective efficacy in mice. Two immunizations of 4-week-old female ICR mice with pcDNA3JEME by intramuscular or intradermal injections at a dose of 10 or 100 microg per mouse elicited neutralizing (NEUT) antibodies at titers of 1:10 to 1:20 (90% plaque reduction), and all immunized mice survived a challenge with 10,000 50% lethal doses of the P3 strain of JE virus. A single immunization with 100 microg of pcDNA3JEME did not elicit detectable NEUT antibodies but induced protective immunity. Spleen cells obtained from BALB/c mice immunized once with 10 or 100 microg of pcDNA3JEME contained JE virus-specific memory cytotoxic T lymphocytes (CTLs). BALB/c mice maintained detectable levels of memory B cells and CTLs for at least 6 months after one immunization with pcDNA3JEME at a dose of 100 microg. The CTLs induced in BALB/c mice immunized twice with 100 microg of pcDNA3JEME were CD8 positive and recognized mainly the envelope protein. These results indicate that pcDNA3JEME has the ability to induce a protective immune response which includes JE virus-specific antibodies and CTLs.

Animals↗

Expermental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. III. In vitro evaluation of cell-mediated immune responses against immune complexes influenced by immunosuppressive therapy.

In this paper, cell-mediated immunity (CMI) as evaluated by in vitro migration inhibition assays an in vivo delayed type skin reactions in experimental immune complex glomerulonephritis (ECGN) was studied as well as the effect of treatment with immunosuppressive drugs on these immune responses. In glomerulonephritic rats MIF production as well as delayed type skin reactions could be demonstrated directed against tubular brushborder antigen (Fx1A) containing immune complexes or to their constituents (FX1A or rabbit IgG). Treatment of the animals with immunosuppressive drugs during settled disease state (autologous phase) abolished these cellular immune reactions. However, neither the glomerular depositions of rat IgG associated with the autologous phase, nor the urinary excretion was influenced. When treatment of the animals was started simultaneously with the induction of the ECGN both cellular and humoral immune responses as well as proteinuria were affected. It was concluded that although in this glomerulonephritis model specific MIF response after specific stimulation in vitro as well as DTH reactions could be detected against immune complexes or their constituents, these immune reactions seem not to play important role in this ECGN in particular with respect to the proteinuria.

Animals↗

Stress, immune regulation, and immunity: applications for asthma.

The neuroendocrine mediators reach the cells of the immune system either through the peripheral circulation or through direct innervation of lymphoid organs. Primary and secondary lymphoid organs are innervated by sympathetic nerve fibers. Lymphocytes and monocytes express receptors for several stress hormones, including CRH, ACTH, cortisol, norepinephrine, and epinephrine. Therefore, it is reasonable to conclude that the neuroendocrine hormones released during a stressful event could alter immune function and subsequently alter the course of immune-based diseases. The impact of psychological stress on immune function has been the subject of extensive research efforts. Using a variety of models from largely healthy humans undergoing various forms of natural and experimental stress models, stress has been associated with suppression of NK activity, mitogen- and antigen-induced lymphocyte proliferation and in vitro production of IL-2 and IFN-gamma. Psychological stress is also associated with a higher rate of in vivo hypoergy to common recall-delayed type hypersensitivity antigens. These studies have suggested that psychological stress suppresses various components of CMI responses. Also, data suggest that chronic stress does not simply suppress the immune system, but induces a shift in the type-1/type-2 cytokine balance toward a predominant type-2 cytokine response. Such a change would favor the inflammatory milieu characteristic of asthma and allergic diseases. Recent studies using well-controlled teenage asthmatic subjects demonstrated immunological changes (decreased NK cell cytotoxicity and cytokine alterations) in response to exam stress. These immune alterations are consistent with a cytokine milieu that could potentially worsen asthma. However, there were no changes in peak flow rates, self-report asthma symptoms, or medication use. The lack of correlation between stress and asthma symptoms may have been related to the timing of the visits in relation to the stressor, the duration of the stressor, disease severity, or a lack of accurate self-report data. Alternatively, stress-mediated exacerbations of asthma may require multiple alterations by stress, including cytokine dysregulation or vagal-mediated airway hyperresponsiveness. The rationale for stress management in asthma is based upon the notion that stress causes a change in immune balance that would favor asthma activity in susceptible individuals. This immune imbalance can be found in TH1/TH2 cytokine changes that occur with stress. Although it has not yet been demonstrated that stress can cause or directly influence the development of asthma, it is interesting to note that both the incidence and prevalence of asthma continue to increase and are higher in urban than in rural areas. Among other differences is the well-appreciated higher chronic stress levels associated with urban living.

Asthma↗

Suppression of immune response and protective immunity to a Japanese encephalitis virus DNA vaccine by coadministration of an IL-12-expressing plasmid.

IL-12 plays a central role in both innate and acquired immunity and has been demonstrated to potentiate the protective immunity in several experimental vaccines. However, in this study, we show that IL-12 can be detrimental to the immune responses elicited by a plasmid DNA vaccine. Coadministration of the IL-12-expressing plasmid (pIL-12) significantly suppressed the protective immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus. This suppressive effect was associated with marked reduction of specific T cell proliferation and Ab responses. A single dose of pIL-12 treatment with plasmid pE in initial priming resulted in significant immune suppression to subsequent pE booster immunization. The pIL-12-mediated immune suppression was dose dependent and evident only when the IL-12 gene was injected either before or coincident with the pE DNA vaccine. Finally, using IFN-gamma gene-disrupted mice, we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenous production of IFN-gamma. These results demonstrate that coexpression of the IL-12 gene can sometimes produce untoward effects to immune responses, and thus its application as a vaccine adjuvant should be carefully evaluated.

Animals↗

DNA immunization with HIV-1 tat mutated in the trans activation domain induces humoral and cellular immune responses against wild-type Tat.

Intramuscular immunization of mice with plasmids encoding two transdominant negative mutants of the HIV-1 Tat protein (Tat22 and Tat22/37) elicited a humoral response to wild-type Tat that is comparable to that induced by inoculation of wild-type tat DNA or Tat protein. The percentage of the responders and the Ab titers continued to increase after three additional DNA boosts and pretreatment with bupivacaine at the site of inoculation, without a significant difference (p > 0.05) among the three groups of mice immunized with mutant and wild-type tat genes. By utilizing synthetic peptides representing the amino acid sequence of Tat, one major B cell epitope was defined within the cysteine-rich domain of Tat. Anti-Tat IgG Abs directed against this epitope were found in mice immunized with all tat DNA constructs, whereas different Tat epitopes were detected in mice immunized with the Tat protein. Similarly, IgG2a was the predominant isotype in DNA-immunized mice, with both mutants and wild-type tat genes, as compared with protein immunization, which induced mostly IgG1 and IgG3. Sera from most immunized mice neutralized the effect of extracellular Tat in activating HIV-1 replication. A cellular response was also elicited as indicated by the proliferation of splenocytes when stimulated with wild-type Tat. These results indicate that the wild-type Tat Ag is recognized by Abs and T cells induced by DNA immunization with mutated tat genes, suggesting the possible use of these Tat transdominant mutants, lacking viral trans activation activity and capable of blocking wild-type Tat activity, in the development of an anti-HIV-1 vaccine.

3T3 Cells↗

Designing immune responses with genetic immunization and immunostimulatory DNA sequences.

Genetic immunization or DNA vaccination represents a rapidly developing technology with new perspectives for the prevention and therapy of infectious diseases and it offers new approaches for the treatment of autoimmunity, tumors and even allergy. DNA vaccines are comprised of plasmid DNA which encodes antigen molecules directly in the transfected cells of a target organism. In contrast to protein-induced immune responses, DNA vaccines stimulate both humoral and cell-mediated immune reactions. In the present review we present a palette of unique features of genetic immunization like the effect of CpG motifs, the influence of mode and site of gene delivery and the modulation of immune responses by co-delivery of cytokines, colony stimulating factors, adhesion molecules and other stimulatory molecules. In addition, modulation of the immune response via translation, processing and presentation will be discussed, which in sum demonstrate the elegant possibilities of genetic immunization to induce tailor-made immune responses.

Animals↗

The Thai expanded programme on immunization: role of immunization sessions and their cost-effectiveness.

A cost-effectiveness study of the Thai expanded programme on immunization was carried out in district hospitals and health centres in Thailand during early 1987. The total annual spending on immunization was US $3852 in hospitals and US $813 in health centres. The percentage distribution of annual costs was similar in both facilities. Salaries were the largest component, followed by building and vaccine costs. The frequency of immunization sessions was the most important factor in determining total costs--immunization costs increasing with the frequency of sessions. In hospitals the average number of fully immunized children was 184, compared with 49 in health centres. The cost per fully immunized child varied widely from US $5.30 to US $33.20, and the most cost-effective facilities were those that immunized the greatest number of children. With the present number of health facilities in all areas of the country, which correspond to saturation levels, the most likely way for the Thai programme to reduce costs would be to make better use of staff time by decreasing the frequency of the services offered, thereby increasing the efficiency of each session. Hospitals should adjust the frequency of their immunization sessions according to the number of children being served, but health centres should offer sessions only monthly or once every two months.

Community Health Centers↗

De novo initiation of specific cell-mediated immune responsiveness in chickens by transfer factor (specific immunity inducer) obtained from bovine colostrum and milk.

Transfer factors (TF) were prepared from colostrum and milk of bovines previously immunized with antigens obtained from Coccidioides immitis, infectious bovine rhinotracheitis virus, or from the viral agents responsible for avian Newcastle disease, laryngotracheitis disease or infectious bursal disease. The ability of bovine TF to transfer specific cell-mediated immune responsiveness to a markedly xenogenic species was studied using specific pathogen free (SPF) and standard commercial (SC) chickens as model recipients. Cell-mediated immune responsiveness was documented using one or more of the following for each antigen (organism) studied: (a) an in vitro chicken leukocyte (heterophil) migration inhibition assay; (b) delayed-wattle reactivity; or (c) protection from clinical disease. Chicken TFs obtained from spleens of immune donors were evaluated in parallel to bovine TF's in selected comparative studies. Bovine TF also referred to as specific immunity inducer (SII), and chicken TF were found to initiate antigen-specific cell-mediated immunity de novo in previously non-immune SPF chickens as well as in SC chickens despite the presence of maternally acquired humoral antibody which may serve as a "barrier" to immunization of SC chickens when commercially available vaccines are administered by parenteral routes. Bovine TF's specific for laryngotracheitis virus or infectious bursal disease virus afforded protection equal to that found for commercially available vaccines. Bovine TF's action was rapid (less than a day) and of relatively long duration at least 35 days.

Animals↗

Concomitant immunization by the fully antigenic counterparts prevents modulated tumor cells from escaping cellular immune elimination.

In a mathematical model of the cellular antitumor immune response, we studied the possible role of antigenic modulation as a tumor escape mechanism. Modulated tumor cells arise from normal (fully antigenic) tumor cells when the latter interact with antibodies. Modulated tumor cells demodulate when antibody concentrations are sufficiently low. Through modulation, tumor cells become less sensitive to cytotoxic macrophages (cell lysis) and contribute less to the stimulation of the immune system. These experimental data are incorporated in a model which we have analyzed previously. The model incorporates interactions between macrophages and T lymphocytes, which lead to cellular antitumor immune reactions (i.e., to cytotoxic macrophages). Parameters were derived from the immune resistance of DBA/2 mice to the SL2 tumor. Although all parameters were chosen deliberately to favor the modulation process (i.e., modulation proceeds fast, demodulation slowly, and the killing rate is reduced 50-fold), modulation is found to be a poor tumor escape mechanism. Heterogeneous populations of modulated and normal tumor cells are easily rejected. Homogeneous populations of modulated cells do escape, however. We conclude that the impact of modulation as an escape mechanism remains small because modulated tumor cells do not appear until the immune system has been stimulated (immunized) by the fully antigenic tumor cells. Thus, the elimination of modulated tumor cells generally occurs merely as a side effect of the immune response which is directed primarily against the fully antigenic tumor cells. Parameter sensitivity analysis shows that this conclusion holds true only for cellular immunity. Conversely, the parameter analysis suggests that antigenic modulation plays a deleterious role in cytotoxic antibody responses (e.g., monoclonal antibody therapy).

Animals↗

Oral immunization with Streptococcus mutants in rhesus monkeys and the development of immune response and dental caries.

The oral route of immunization with Streptococcus mutants was compared with the subcutaneous route in rhesus monkeys. Significant levels of serum IgG, IgM and IgA antibodies in Strep. mutans were elicited only in monkeys immunized subcutaneously. Similarly, the skin delayed hypersensitivity reaction to Strep. mutans was elicited only in the subcutaneously immunized monkeys. Oral immunization induced a modest increase in salivary IgA antibodies to Strep. mutans, though a slight increase in IgA antibodies was also found in the saliva of all other groups of immunized and control monkeys. A small though not significant reduction in dental caries was found in the monkeys immunized orally, whereas subcutaneous immunization with Strep. mutans consistently elicited a significant reduction in caries. Oral feeding of Strep. mutans failed to induce tolerance to a subsequent subcutaneous challenge by the same organism. Furthermore, sequential subcutaneous followed by oral immunization had little effect on the titre of salivary or serum antibodies.

Administration, Oral↗

[Relationship between orally induced immune tolerance and local immune response (author's transl)].

BALB/c mice were immunized by intragastric immunization with sheep red blood cells repeated daily for 4 days. This immunization resulted in the appearance of circulating antibodies which were predominantly of the IgA class. When serum from intragastrically immunized mice was administered intraperitoneally to recipient animals 8 h before parenteral immunization with sheep red blood cells, the subsequent immune response was depressed proportionally to the dose of serum injected. When intragastrically immunized mice were challenged intraperitoneally with sheep red blood cells, the level of the IgM response to the parenteral stimulation was in inverse ratio to the IgA response induced by the oral route. These results suggest that orally induced IgA production is related to orally induced immune tolerance and that systemic hyporesponsiveness is achieved while gut plasma cells are producing specific IgA.

Administration, Oral↗

General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP).

This revision of the General Recommendations on Immunization updates the 1989 statement. Changes in the immunization schedule for infants and children include recommendations that the third dose of oral polio vaccine be administered routinely at 6 months of age rather than at age 15 months and that measles-mumps-rubella vaccine be administered routinely to all children at 12-15 months of age. Other updated or new sections include a) a listing of vaccines and other immunobiologics available in the United States by type and recommended routes, advice on the proper storage and handling of immunobiologics, a section on the recommended routes for administration of vaccines, and discussion of the use of jet injectors; b) revisions in the guidelines for spacing administration of immune globulin preparations and live virus vaccines, a discussion of vaccine interactions and recommendations for the simultaneous administration of multiple vaccines, a section on the interchangeability of vaccines from different manufacturers, and a discussion of hypersensitivity to vaccine components; c) a discussion of vaccination during pregnancy, a section on breast-feeding and vaccination, recommendations for the vaccination of premature infants, and updated schedules for immunizing infants and children (including recommendations for the use of Haemophilus influenzae type b conjugate vaccines); d) sections on the immunization of hemophiliacs and immunocompromised persons; e) discussion of the Standards for Pediatric Immunization Practices (including a new table of contraindications and precautions to vaccination), information on the National Vaccine Injury Compensation Program, the Vaccine Adverse Events Reporting System, and Vaccine Information Pamphlets; and f) guidelines for vaccinating persons without documentation of immunization, a section on vaccinations received outside the United States, and a section on reporting of vaccine-preventable diseases. These recommendations are based on information available before publishing and are not comprehensive for each vaccine. The most recent Advisory Committee on Immunization Practices (ACIP) recommendations for each specific vaccine should be consulted for more details.

Adolescent↗

Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status. Centers for Disease Control and Prevention Vaccine Safety Datalink Group.

CONTEXT: Studies have noted that health care professionals may not conform to proper immunization schedules for premature and low-birth-weight infants in the United States. Little is known about the success of current efforts to immunize these high-risk infants. OBJECTIVE: To describe current immunization practices for premature and low-birth-weight infants and ascertain risk factors for poor immunization status, using large population-based data sources. DESIGN AND SETTING: Cohort and case-control analyses of immunization data tracked from March 1991 through March 1997 for 3 large health maintenance organizations (HMOs) participating in the Centers for Disease Control and Prevention's Vaccine Safety Datalink project. PARTICIPANTS: A total of 11580 low-birth-weight and premature infants were enrolled from birth to age 2 months; 6832 of these were continuously enrolled from birth to age 24 months. At age 2 months, there were 173373 full-term, normal-birth-weight infants enrolled as controls; at age 24 months, there were 103 324. MAIN OUTCOME MEASURES: Age-specific immunization status by prematurity and birth weight (<1500 g, 1500-2500 g, born at <38 weeks' gestation with birth weight of >2500 g, or full-term with normal birth weight) and patient characteristics associated with up-to-date status. RESULTS: At each age, infants weighing less than 1500 g at birth had lower up-to-date immunization levels than other infants. At age 6 months, 52% to 65% of infants weighing less than 1500 g were up-to-date at each of the 3 HMOs compared with 69% to 73% of those weighing 1500 to 2500 g, 66% to 80% of premature infants weighing more than 2500 g, and 65% to 76% of full-term, normal-birth-weight infants. By age 24 months, 78% to 86% of infants weighing less than 1500 g were up-to-date, significantly less than heavier infants, who had levels of 84% to 89%. Well-child preventive care strongly predicted immunization status, while concomitant pulmonary disease did not. CONCLUSIONS: Our data suggest that infants born prematurely are vaccinated at levels approaching that of the general population, but levels of vaccination for very low-birth-weight infants lag slightly behind.

Health Maintenance Organizations↗

Oral immunization of swine with attenuated Salmonella typhimurium aroA SL3261 expressing a recombinant antigen of Mycoplasma hyopneumoniae (NrdF) primes the immune system for a NrdF specific secretory IgA response in the lungs.

Salmonella typhimurium SL3261 (aroA mutant) expressing a recombinant Mycoplasma hyopneumoniae antigen was used to orally immunize swine against porcine enzootic pneumonia. This construct, designated S. typhimurium aro A SL3261 (pKF1), expressed a recombinant protein containing the carboxy-terminal 11 kDa of a 42 kDa M. hyopneumoniae NrdF ribonucleotide reductase R2 subunit protein. Here we demonstrate that this antigen is present in all seven geographically diverse strains of M. hyopneumoniae tested, and is recognized by the swine immune system after experimental infection with the virulent M. hyopneumoniae Beaufort strain. The immune response of swine orally immunized twice with S. typhimurium SL3261 (pKF1) on day 0 and day 14 was evaluated. Oral immunization with S. typhimurium SL3261 (pKF1) primed the immune system to elicit a significant (P<0.05) secretory IgA response against the 15 kDa NrdF antigen in the respiratory tract of swine, post-challenge, compared to control groups. Blood lymphocytes from swine immunized with S. typhimurium SL3261 (pKF1) proliferated significantly (P<0.05) following stimulation with M. hyopneumoniae whole-cell extracts compared to control groups 14 days post-vaccination. Following challenge with virulent M. hyopneumoniae, swine immunized with S. typhimurium SL3261 (pKF1) showed higher average daily weight gains and reduced lung pathology compared to control groups.

Administration, Oral↗