Immunoglobulin A Response Research Articles

Antibody responses to Toxoplasma gondii in sera, intestinal secretions, and milk from orally infected mice and characterization of target antigens

Toxoplasma gondii-specific antibody responses in serum, intestinal secretions, and milk were identified with an enzyme-linked immunosorbent assay following a single oral infection of mice with strain 76K cysts of T. gondii. Immunoglobulin A (IgA) production began during week 2 of infection in serum and milk and during week 3 of infection in intestinal secretions and persisted in all three throughout the experiment (17 weeks). IgG but not IgM antibodies were detected in intestinal secretions later in the infection. Serum and milk IgG and IgM production began at the same time after infection as did the IgA response. In Western blotting (immunoblotting), intestinal IgA antibodies were shown to react with antigens comigrating with the T. gondii proteins p22, p23, p30, and p43, the 28-kilodalton antigen, and the 55- and 60-kilodalton rhoptry proteins, as recognized by specific monoclonal antibodies. Milk IgA antibodies reacted with antigens comigrating with p30 and p43. Most of the antigens recognized by IgA antibodies were also detected by IgG antibodies. IgA antibodies from all three biological samples detected the same major T. gondii antigens; thus, there was apparently no specific antibody production unique to one locality.

Immunoglobulin A and immunoglobulin G antibody responses to alginates from Pseudomonas aeruginosa in patients with cystic fibrosis

Patients with cystic fibrosis have a high prevalence of mucoid, alginate-producing Pseudomonas aeruginosa that causes chronic infection of the mucosal surface of the lungs. We developed enzyme-linked immunosorbent assays (ELISAs) for determination in serum of immunoglobulin A (IgA) and IgG antibodies to alginate purified from P. aeruginosa and an ELISA for detection of IgA antibodies to a polyvalent P. aeruginosa standard antigen. Absorption experiments indicated that the assays were antigen and antibody specific and had analytical variations that ranged from 7 to 19%. Serum samples from 207 patients with cystic fibrosis, 100 healthy children, and 94 healthy adults were examined. The patients responded to P. aeruginosa infection with early IgA and IgG antibody responses that were significantly higher than in controls and noncolonized patients. Analysis of paired serum samples showed that infected patients had an increase in specific IgG and IgA antibodies that was significantly higher than in noncolonized patients. The serological data were analyzed for correlation with clinical condition; poor lung function was significantly associated with increased levels of IgA and IgG antibodies to P. aeruginosa alginate and to the standard antigen and with a relative excess of IgA antibodies to the standard antigen compared with IgA antibodies to P. aeruginosa alginate. The assays showed high predictive values if positive, but a negative test did not exclude infection, and the ELISAs should not be used for diagnostic purposes. Mucoid strains were present initially in the sputa of 28 of 54 infected patients with paired serum samples. These patients had a significant increase in anti-alginate antibodies, but it was not different from the increase seen in patients infected only with nonmucoid strains. Therefore, alginate may also be produced in vivo by nonmucoid P. aeruginosa. The study showed that early formation of IgA and IgG antibodies to P. aeruginosa alginate did not prevent development of chronic infection and that P. aeruginosa-specific IgA antibodies correlate with poor lung function.

Elevated membrane IgA + and CD4 + (T helper) populations in murine peyer's patch and splenic lymphocytes during dietary administration of the trichothecene vomitoxin (deoxynivalenol)

Recent investigations indicate that dietary exposure to the trichothecene vomitoxin increases total and antigen-specific serum immunoglobulin A (IgA) and glomerular IgA accumulation in mice. In this study, the effects of 25 ppm dietary vomitoxin on the histological and lymphocytic profile of component immune organs in the mucosal lymphocyte migratory pathway were evaluated in the B6C3F 1 mouse. Vomitoxin administration resulted in marked stimulation of the size and frequency of germinal centres in Peyer's patches, mesenteric lymph nodes and the spleen. A slight increase in the percentage of B cells in the Peyer's patch was observed, although vomitoxin treatment had no effect on the percentage of B cells in the spleen. The percentage of IgA + cells in Peyer's patches and spleen were approximately twice that of controls at 4, 8 and 12 wk of vomitoxin exposure whereas the percentage of IgG + cells decreased in these two organs. Exposure to vomitoxin increased the percentage of T cells in Peyer's patches and the spleen. The percentage of CD4 + cells (T helper subset) increased slightly in Peyer's patches and more markedly (30–50%) in the spleen following vomitoxin treatment. Contrastingly, there was only a slight increase in the percentage of CD8 + cells (T cytotoxic/suppressor subset) in the spleens of vomitoxin-treated mice in comparison with controls, and no effect in Peyer's patches. The relative effects of vomitoxin on these two T cell populations was also reflected in increased CD4 +:CD8 + ratios in Peyer's patches and spleen. These results are consistent with the hypothesis that dietary vomitoxin modulates normal regulation of the IgA response at the Peyer's patch level and that this is manifested in an altered lymphocyte distribution pattern in both the mucosal and systemic compartment. Notably increased levels of IgA + and CD4 + cells are indicative of IgA-producing progenitors and T helper subsets, respectively, that in tandem could favour IgA hyperproduction and elevated IgA in serum.

Immunoglobulin A antibody response to respiratory syncytial virus structural proteins in colostrum and milk

Immunoglobulin A (IgA) antibody response to respiratory syncytial virus (RSV) structural proteins in colostrum and milk was investigated by a radioimmunoprecipitation assay. By using [35S]methionine-labeled RSV-infected HEp-2 cells and antiserum to human IgA as the capture antibody, IgA antibody responses to large glycoprotein, fusion protein, nucleoprotein, phosphoprotein, and matrix protein were demonstrated in colostrum and milk. The IgA antibody response was mainly directed against fusion protein, whereas IgA activity against matrix protein was more variable and was not comparable to the antibody responses to other structural proteins. Maternal mammary IgA response after RSV infection in the infant was monitored in four cases, and the appearance of anti-RSV IgA activity against several RSV structural proteins was observed in convalescent-stage milk samples of two mothers in whom RSV infection was demonstrated.

Secretory immunoglobulin A response to Shiga toxin in rabbits: kinetics of the initial mucosal immune response and inhibition of toxicity in vitro and in vivo.

Although the role of Shiga toxin in dysentery is unknown, the toxin is cytotoxic to HeLa cells, causes fluid secretion in rabbit intestine, and is lethal to rabbits and mice when injected parenterally. In the present study, rabbits received three weekly doses of Shiga toxin directly into chronically isolated ileal loops. Within a week, secretions from these loops contained immunoglobulin A (IgA) anti-Shiga toxin. The titer of IgA anti-Shiga toxin increased after weekly doses 2 and 3. Little IgG anti-Shiga toxin was present in loop secretions, although high titers of IgG anti-Shiga toxin were found in the sera. These loop secretions were able to neutralize the cytotoxic effects of Shiga toxin in the HeLa cell assay. The capacity to neutralize the cytotoxicity of the toxin correlated strongly with the IgA anti-Shiga toxin titer in these same secretions. Pooled immune loop secretions were also able to significantly reduce fluid accumulation in acutely ligated loops in rabbits, while loop secretions from control rabbits could not. Shiga toxin elicited a strong secretory IgA response upon application to the intestine. Further, the mucosal antibodies produced functioned to prevent the toxic effects of Shiga toxin both in vitro and in vivo.

Respiratory syncytial virus-specific antibody responses in immunoglobulin A and E isotypes to the F and G proteins and to intact virus after natural infection.

We studied the antibody response to the fusion (F) and attachment (G) proteins of respiratory syncytial virus and to purified intact virus in the respiratory secretions of 29 infants and children. The goal of the study was to determine whether the immune response to either of the glycoproteins occurred predominantly in the immunoglobulin A (IgA) as opposed to the IgE isotype, which would indicate that one protein subunit would be a better candidate as a potential vaccine. Antibody responses were determined by using an enzyme-linked immunosorbent assay with purified F and G proteins and sucrose gradient-purified intact virus as targets. Infants and children were capable of developing an antibody response in both the IgA and IgE isotypes to each target antigen. The magnitude of the antibody response to the F protein was essentially similar to that to the intact virus, while responses to the G protein were diminished in infants. A slightly more favorable ratio of IgA to IgE responses was observed against the F protein in comparison to the G protein. While neither protein subunit had the ideal characteristics of inducing an IgA response in the absence of an IgE response, the F protein seems to be a better candidate for use as a vaccine, on the basis of better IgA/IgE ratios.

Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough.

Specific immunoglobulin A (IgA) to Bordetella pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) was determined in mucosal secretions by an enzyme-linked immunosorbent assay (ELISA). It took 3 to 4 h to complete the ELISA. The upper limits of normal values for age were determined in nasopharyngeal (NPH) secretions from 23 patients with viral infections and in 10 healthy adults working with pertussis patients or cultures. A significant IgA response to FHA was found in 38 of 54 (70%) and to PT in 28 of 54 (52%) NPH secretions from patients with pertussis confirmed by culture, serology, or both. The rate of positive responses to either antigen (44 of 54 [81%]) was significantly higher than that by culture alone (29 of 54 [54%]; P less than 0.01). The rate of positive responses increased from 65% in patients with symptoms for 1 week or less to 87 to 92% in patients with symptoms for 2 or more weeks. The specific IgA response to PT was found in 100% of NPH samples from 17 unimmunized children less than 3 years of age and in only 30% of adults and immunized children greater than 3 years of age. A response to FHA was found in 65 to 73% of the NPH secretions in all age groups. Saliva samples were found to contain specific IgA to FHA and PT in all age groups, but these were of diagnostic value in 50% (11 of 22) of the adult patients. The specificity of the ELISA was 100% (10 of 10 negatives) in NPH secretions from patients with pertussis-like cough who had negative cultures and serology. The results indicate that determination of specific IgA to PT and FHA in NPH aspirates represents a sensitive and rapid diagnostic method for the detection of pertussis.

Combined parenteral and oral immunization results in an enhanced mucosal immunoglobulin A response to Shigella flexneri.

Achieving a vigorous secretory immunoglobulin A (IgA) response in intestinal secretions usually requires multiple doses of antigen given orally, while systemic immunity is more easily attained by parenteral immunization. This study examines the role of combined parenteral and oral immunizations to enhance the early mucosal immune response to an enteropathogen. We have used a chronically isolated intestinal-loop model in rabbits as a probe to monitor kinetically the initial (primary) local immune response to shigella lipopolysaccharide (LPS) following combinations of parenteral immunization intramuscularly (i.m.) and oral stimulation with shigellae. Predictably, effective stimulation of systemic immunity was elicited when heat-killed preparations of Shigella sp. strain X16 were given i.m., as shown by strong serum IgG and weak intestinal IgA activity to shigella LPS. A single oral dose of live Shigella sp. strain X16 given to unprimed rabbits elicited only a typical weak IgA response in intestinal secretions. However, when an i.m. dose of heat-killed shigellae was followed 1 day later by an oral dose of live Shigella sp. strain X16, a hyperstimulation of the early secretory IgA response was elicited, and the response reached levels found previously only after multiple oral administrations of live shigellae. This stimulation did not require the use of an adjuvant. At the same time, the animals receiving this combined oral and i.m. regimen had a lower IgG antishigella LPS activity in serum compared with their response after receiving parenteral antigen in adjuvant alone. These findings indicate that while a dichotomy exists between the systemic and mucosal immune responses, careful orchestration of the stimulatory events can promote a vigorous early local IgA response.

Modulation of murine Peyer's patch immunoglobulin A response by enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) may have profound effects on the capacity of gut-associated lymphoid tissue to mount a secretory immune response because of the potential ability of heat-stable toxin or heat-labile toxin to modulate the immune response. To examine the effects of ETEC or its purified enterotoxins upon the humoral immune response of murine small intestinal Peyer's patch lymphocytes, BDF1 (lipopolysaccharide-responder) and C3H/HeJ (lipopolysaccharide-nonresponder) mice were orally primed with sheep erythrocytes (SRBC) four times during a 2-week period to initiate differentiation of Peyer's patch B lymphocytes to cells committed to anti-SRBC immunoglobulin A (IgA) production. Halfway through the oral priming regimen the mice were gastrically intubated with 10(8) ETEC, 10(8) non-ETEC, or saline. ETEC persisted in the small intestine for at least 7 days at a level of 10(3) to 10(4) bacteria per mouse. Seven days after the last oral dosing with SRBC, Peyer's patch lymphocytes were removed from infected or saline-treated mice and incubated in vitro with SRBC. The ETEC infection had a small effect on the anti-SRBC IgM plaque-forming cell response of SRBC-primed mice but inhibited significantly the anti-SRBC IgA plaque-forming cell response in both BDF1 and C3H/HeJ mice as compared with uninfected controls. The non-ETEC, an isolate from normal mouse small intestine, had no significant effect on either IgM or IgA anti-SRBC plaque-forming cell response. Purified heat-labile toxin, not heat-stable toxin, alone in a dose-dependent manner significantly inhibited both the IgA and IgM plaque-forming cell response of Peyer's patch lymphocytes from primed mice. These data suggest that ETEC can inhibit the development of the gut-associated lymphoid tissue IgA immune response through the immunopharmacological effect of an enterotoxin, the heat-labile toxin.

Determinants of the immunogenicity of live virulent and mutant Vibrio cholerae O1 in rabbit intestine

Determinants of the capacity of live Vibrio cholerae O1 isolates to evoke specific immune responses in intestinal mucosa were studied in rabbits, using mucosal immunoglobulin A (IgA) antitoxin as the measured immune response. Antitoxin responses were evoked mostly by the primary inoculation and were dose dependent; secondary-type responses were modest and occurred only when the booster inoculum was large, i.e., 10(10) CFU. The efficiency of mucosal immunization correlated closely with the mucosal colonizing capacity of the infecting strain and was otherwise independent of toxin genotype (A+ B+ or A- B+) or whether the strain was motile or nonmotile. Live bacteria evoked mucosal antitoxin more efficiently than did purified cholera toxin. Prior immunization with a nontoxinogenic (A- B-) V. cholera strain interfered significantly with the induction of mucosal antitoxin by subsequent immunization with its fully toxinogenic (A+ B+) parent. These results demonstrate the marked efficiency with which live V. cholerae stimulate a specific enteric mucosal secretory IgA response. They support the view that mucosal colonization aids efficient delivery of bacterial antigens to responsive subepithelial lymphoid tissue. This might occur by transfer of colonizing bacteria through M cells into Peyer patches or by efficient delivery of secreted toxin to M cells by mucosa-associated organisms. Preexisting antibacterial immunity interferes with colonization, which may prevent efficient antigenic stimulation and which may explain the relatively weak response to booster immunization. The same process may also limit the efficacy of hybrid enteric bacterial vaccines when there is preexisting mucosal immunity to the carrier organism due to either natural exposure or prior immunization with another vaccine that uses the same carrier.

Induction of mucosal immunoglobulin A immune response by preparations of Neisseria gonorrhoeae porin proteins.

The aim of this study was to develop an immunization scheme appropriate for the induction of an immunoglobulin A (IgA) response against Neisseria gonorrhoeae at the mucosae. For several reasons, the major outer membrane protein of N. gonorrhoeae (gonococcal PI) is attractive as a component of a gonococcal vaccine. Purified PI obtained from strain B2 was used in Zwittergent 3-14 for immunization. Rats received the antigen subcutaneously, intraintestinally, or directly in Peyer's patches with or without the adjuvant N-acetylmuramyl dipeptide (MDP) or AlPO4. The immune response was studied in situ by a newly developed antigen-specific three-step immunoperoxidase method, whereas specific antibodies in the serum were measured by an enzyme-linked immunosorbent assay procedure. Subcutaneous immunizations triggered peripheral lymphoid organs, whereas intraintestinal and intra-Peyer's patch immunizations triggered mucosa-associated lymphoid organs. This was reflected not only in the lymph nodes involved, popliteal versus mandibular and mesenteric lymph nodes, but also in the isotypes of the produced anti-PI antibodies, IgG versus IgA. The adjuvants AlPO4 and MDP appeared to act differently during subcutaneous and intraintestinal immunizations. AlPO4 augmented subcutaneous immune responses, whereas MDP had no effects. In contrast, intraintestinal immune responses increased most with the adjuvant MDP. In summary, we concluded that PI is capable of inducing a mucosa-associated IgA response when administered intraintestinally and that this response can be augmented by the adjuvant MDP.

Tear and serum antibody response to Chlamydia trachomatis antigens during acute chlamydial conjunctivitis in monkeys as determined by immunoblotting.

In this study, we examined the temporal antibody response by immunoblotting analysis in tears and sera of three cynomolgus monkeys (Macaca fasicularis) with primary acute Chlamydia trachomatis serovar B conjunctivitis. The objective was to identify chlamydial antigens stimulating antibody during the host responses in the course of this self-limiting infection with the rationale that they may be protective antigens. The major outer membrane protein (MOMP), lipopolysaccharide (LPS), and polypeptides of 60 and 68 kilodaltons (kDa) were the predominant antigens recognized by immunoglobulin A (IgA) in monkey tears. Tear IgA antibody specific for the MOMP was first detected 14 days postinfection, whereas tear IgA reactive with LPS or the 68- and 60-kDa polypeptides was first detectable on day 21. Tear IgA antibodies specific for each of these antigens persisted in tears through day 56, 4 weeks after both peak clinical disease and recovery of the organism from the conjunctivae. In contrast, tear IgG antibodies peaked at approximately 28 days postinfection, the time of maximal inflammatory response. The IgG response in monkey sera was similar to that observed for tear antibodies, in that the MOMP, 60-, and 68-kDa polypeptides were the primary immunogens. The exception was that IgG antibody against these antigens was detected 1 week later than that observed for tear IgA antibodies. Of three monkeys that responded with tear IgA antibody against LPS, one did not have detectable serum IgG LPS antibody. The specificity of the tear IgA antibody response of monkeys was determined by immunoblotting nine other C. trachomatis serovars in addition to the homologous B serovar. The tear IgA response to the MOMP was predominantly B complex subspecies-specific (serovars B, Ba, D, and E), whereas the response to chlamydial LPS was found to be species-specific. The significance of these observations in relation to previous vaccine studies in nonhuman primates is discussed.

Transfer of immunity to Ostertagia circumcincta and IgA memory between identical sheep by lymphocytes collected from gastric lymph

Sheep rendered immune to Ostertagia circumcincta were challenged with 50,000 larvae and lymphocytes were collected from the gastric lymph up to eight days after challenge. The cells were transferred intravenously to genetically identical worm-free sheep which, together with controls, were challenged with 50,000 larvae and killed nine days later. Cells obtained during the donors lymphoblast response to challenge transferred partial immunity, measured either as stunting or loss of worms. Significantly less immunity was transferred by cells collected either before or after this response. Thus the responding cells can mediate protective immunity to O circumcincta. On the other hand the donor sheep remained immune to their challenge infection despite being depleted of these functional cells, showing that their presence was not essential for immunity to be maintained. Comparison of the immunoglobulin A (IgA) concentrations in the gastric lymph of recipient and control sheep showed that a local IgA response had also been transferred. Enumeration of mucosal mast cells suggested that a mastocytosis had been transferred to the two recipients which were most immune to challenge.

Saliva, breast milk, and serum antibody responses as indirect measures of intestinal immunity after oral cholera vaccination or natural disease.

The possibility that antibody responses in serum, saliva, or breast milk samples to oral vaccines or enteric infections may reflect the intestinal immune response was evaluated in Bangladeshi volunteers orally immunized with a cholera B subunit-whole-cell vaccine (B + WCV) and in patients convalescing from enterotoxin-induced diarrheal disease. Two peroral doses of B + WCV induced antitoxin and antibacterial antibody responses in the intestinal fluids of 76 and 92%, respectively, of the volunteers and in serum samples in 90 and 69% of those tested. These responses were comparable to those obtained after cholera or enterotoxigenic Escherichia coli disease. Whereas immunoglobulin A (IgA) antitoxin titer increases in saliva (44%) and breast milk (29%) specimens after vaccination were less frequent than in intestinal fluid (76%), antitoxin responses in saliva and breast milk occurred in 80 to 90% of the patients after disease. Also, antilipopolysaccharide (anti-LPS) titer increases in extraintestinal body fluids were found more frequently after disease than after vaccination. A comparison of the frequency and magnitude of antibody response in different body fluids with those in intestinal lavage fluid revealed no extraintestinal antibody that directly reflected the intestinal immunity. However, comparison of vibriocidal and IgG antitoxin antibodies in serum specimens with antitoxin and anti-LPS IgA responses in intestinal fluids after the vaccination of volunteers showed a sensitivity of 70 to 90% and a predictive accuracy of about 80% for the serum analyses reflecting the intestinal immune responses. Furthermore, antitoxin and anti-LPS antibody responses in saliva and breast milk samples seemed to be useful proxy indicators of a gut mucosal response of these antibodies after enterotoxin-induced diarrheal disease showing sensitivity vales of 70 to 90% and predictive accuracy vales of 70 to 100%.

Serum and salivary antibody responses in rats orally immunized with Streptococcus mutans carbohydrate protein conjugate associated with liposomes.

In this study we describe the preparation of a Streptococcus mutans vaccine consisting of a purified polysaccharide antigen, derived from S. mutans OMZ175 serotype f, covalently coupled through reductive amination to a previously isolated 74,000-molecular-weight (74K) cell wall protein which interacts with saliva proteins (74K-SR). We also investigated the local and systemic immune response to the poly-74K-SR conjugate after oral administration of the conjugate associated with liposomes. Intragastric administration of liposome-associated poly-74K-SR conjugate in rats produced a local immunoglobulin A (IgA) response directed against the polysaccharide and the cell surface protein, whereas liposome-associated polysaccharide was unable to induce any detectable local IgA response. The antigenicity of the polysaccharide in the conjugate was not affected by the coupling reaction, while that of the cell surface protein was reduced. We showed that the immunogenicity of S. mutans polysaccharide could be improved by chemical coupling with a carrier cell surface protein. If such a conjugate were orally administered with liposomes it could constitute a potential vaccine against dental caries.

Administration of purified colonization factor antigens (CFA/I, CFA/II) of enterotoxigenic Escherichia coli to volunteers: Response to challenge with virulent enterotoxigenic Escherichia coli

Colonization factor antigens (CFAs) were administered orally to volunteers, and the mucosal immune response was assessed by measuring secretory immunoglobulin A (IgA) in saliva and intestinal secretions and by challenge with virulent enterotoxigenic Escherichia coli (ETEC). A combination of CFA/I and CFA/II (8 mg each) administered orally in four doses in milk failed to induce a mucosal IgA response and also failed to protect against challenge with CFA-positive ETEC. When CFA was administered orally (1.5 mg divided into three doses with bicarbonate) to volunteers without preexisting serum anti-CFA levels, it failed to elicit a serum IgG or intestinal secretory IgA response or to protect against challenge with virulent ETEC. The CFA is destroyed by acid gastric contents but it induced significant antibody titer rises in 8 of 11 (73%) volunteers with preexisting serum anti-CFA IgG levels after oral administration of 1 mg of CFA/I with sodium bicarbonate. Subcutaneous priming (50 μg CFA/I) did not induce a serum IgG response but, when followed by oral boosting (1 mg CFA/I in two divided doses with sodium bicarbonate), induced intestinal anti-CFA secretory IgA in 4 of 8 volunteers and protected against challenge with CFA/I-positive ETEC. These results, although preliminary, are encouraging and demonstrate that it may be possible to develop an effective oral vaccine based on soluble nonreplicating antigens such as purified CFAs.

Effect of parenteral immunization on the local immunoglobulin A response of the intestine to Shigella flexneri antigens.

Most traditional methods of immunization involve parenteral vaccines. Using a chronically isolated ileal loop model as the probe, we examined the effect of a primary parenteral immunization on the local immune response of the intestine. Secretions from isolated ileal loops of rabbits given a primary parenteral immunization with Shigella flexneri without adjuvant showed a small, but definite, specific immunoglobulin A (IgA) response locally, whereas a vigorous serum antigen-specific IgG response was elicited. Also, stronger antigen-specific IgG activity was detected in secretions of parenterally immunized animals than from animals given shigella only by oral immunization. No local IgA or IgG memory response could be elicited by prior parenteral priming with S. flexneri antigens. Lastly, no increase in the primary local IgA response was found in secretions from animals given an oral dosage regimen previously shown to prime for mucosal memory and then challenged with a single parenteral dose of the same antigen. These studies demonstrate that without adjuvant, parenteral doses of S. flexneri antigens elicit both specific serum and local immune responses, but they are not able to prime for a mucosal memory response upon subsequent mucosal challenge. The implications of these findings for programs that use parenteral vaccination to protect against mucosal diseases are discussed.

Salivary immunoglobulin A antibodies and recovery from challenge of Streptococcus mutans after oral administration of Streptococcus mutans vaccine in humans.

Heat-killed Streptococcus mutans was administered orally in two periods of 1 week to six subjects in an attempt to affect the salivary immunoglobulin A (IgA) response to this bacterium. Enzyme-linked immunosorbent assays were used to detect specific IgA antibody activity, and an immunofluorescent assay was used for measurement of total IgA in parotid saliva. The salivary IgA response to S. mutans was compared with that against a noncross-reacting antigen preparation from Escherichia coli and with antibody responses in five sham-immunized subjects. No change in salivary IgA response to S. mutans was observed after oral administration of this organism. Significantly less streptomycin-resistant S. mutans could be recovered from the six test subjects than from the five controls after the first of two challenges with streptomycin-resistant microorganisms. At the day of the first challenge, a significantly higher IgA antibody response to all tested antigens was observed in the test group than in the control group. The data show that this difference was not related to the oral administration of S. mutans but rather was an occasional finding. The coincidence of a rapid elimination of the challenge strain and a high IgA antibody response to S. mutans supports the concept that salivary IgA antibodies could have a biological significance in the human defense against cariogenic microorganisms.