Kinetics of antigen-specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients

Understanding of kinetics of antibody responses is crucial for developing rapid serological tests and studying the mechanisms of Zika virus (ZIKV) infection. Most of the serological diagnostic assays previously published are based on either IgM or IgG titer, little is known on the level of IgA antibody in saliva and urine. In this study, we investigated the kinetics of IgM/IgG/IgA antibody responses in serum, saliva, and urine obtained from two ZIKV infected individuals from as early as the second day of onset of symptoms to as long as 2 years postinfection. Other than detecting robust early IgM response, long lasting IgG response, we discovered strong early IgA response specific for ZIKV in saliva in both patients. This unique observation provides a novel strategy and scientific basis for the development of noninvasive rapid tests for ZIKV infection.     

EB病毒蛋白诱导IgG和IgM产生的作用

目的:检测热灭活或紫外线(UV)灭活的EB病毒(EBV)刺激培养的人脐带血B细胞产生IgG和IgM的效应。方法:常规分离人脐带血单个核细胞(UBMC),以L-亮氨酸甲酯去除法,去除单核细胞、NK细胞和细胞毒性T细胞,以2-氨乙基硫脲溴化物(AET)处理绵羊红细胞(SRBC)的花环形成分离法,去除T细胞以获得纯化的B细胞。分别用UV和热灭活的EBV刺激培养的B细胞后,用夹心ELISA法检测培养上清中IgG 和IgM的产生。结果:以UV灭活的EBV刺激培养B细胞后18 d起,IgG和IgM的产生具有意义(P<0.05);而热灭活的EBV刺激后,各时间点均无显著差异(P>0.05)。结论:UV灭活EBV具有诱导IgG和IgM产生的作用,但有明显的时效性,提示EBV诱导IgG和IgM产生,可能是通过病毒的蛋白成分实现的,为进一步验证EBV功能蛋白诱导天然自身抗体(NAA)产生中的作用奠定了基础。     

Solid-phase radioimmunoassay of IgA, IgG, and IgM antibodies to human rotavirus.

A solid-phase radioimmunoassay (RIA) has been developed for the detection of human rotavirus-specific IgA, IgG, and IgM antibodies. Nebraska calf diarrhea virus grown in LLC-MK2 cell cultures in the presence of trypsin was directly adsorbed onto polystyrene balls, and antibodies that attached to the virus-coated balls were detected by subsequent binding of 125I-labeled antibodies specific to human alpha, gamma or mu chains of human Iga, IgG, or IgM immunoglobulins. A total of 116 serum specimens from 58 adult patients were tested. Binding ratios between the positive and the negative serum varied between 5 and 15, occasionally being 20 or more in the IgA and IgG assays, but rarely exceeding 3 in the IgM assay. The RIA was found to be more sensitive in detecting antibodies to rotavirus than the complement fixation (CF) test, the RIA titers obtained being 50--100 times as high as the CF titers. The method described offers a possibility of evaluating the immune response to human rotavirus and of detecting recent infection.     

Chronological evolution of IgM, IgA, IgG and neutralisation antibodies after infection with SARS-associated coronavirus

Abstract Serum levels of IgG, IgM and IgA against severe acute respiratory distress syndrome (SARS)-associated coronavirus (SARS-CoV) were detected serially with the use of immunofluorescent antibody assays in 30 patients with SARS. Seroconversion for IgG (mean 10 days) occurred simultaneously, or 1 day earlier, than that for IgM and IgA (mean 11 days for both). IgG could be detected as early as 4 days after the onset of illness. The earliest time at which these three antibodies reached peak levels was similar (mean 15 days). A high IgG level (1:800) could persist for > 3 months. The kinetics of neutralisation antibodies obtained with 100x the tissue culture infective dose (TCID50) of the SARS-CoV TW1 strain in five patients with SARS nearly paralleled those for IgG. There were no significant differences in the kinetics of the IgG, IgM and IgA responses between patients with or without underlying medical disease, steroid or intravenous immunoglobulin therapy, or mechanical ventilation.     

Competitive inhibition enzyme immunoassays for the measurement of human IgG, IgA and IgM

Competitive-inhibition enzyme immunoassays for the measurement of human IgG, IgA and IgM are described. These assays can be readily performed with commercial antisera and a recently developed method for purifying human IgA and IgM with high yield. The assays described are specific, with undetectable (<0.5%) cross-reactivity between the immunoglobulin classes in all systems, except with purified IgM, which cross-reacted to 1.9% with the IgG enzyme immunoassay.Minimal detectable concentrations of 2.5±0.8 ng/ml for IgG 4.2±0.9 ng/ml for IgA and 7.2±1.4 ng/ml for IgM were recorded, indicating that these assays are particularly sensitive. There is little within-assay variation (mean coefficient of variation = 3.9%), although the between-assay variation was substantially greater (mean coefficient of variation = 23.5%). These assay systems appear to be particularly suited to the measurement of immunoglobulin production by lymphocytes in culture. In such studies the assay must be specific, sensitive and be capable of discriminating between levels of immunoglobulin produced in response to various experimental treatments.     

Interleukin-2 correction of defectivein vitro T-cell mitogenesis in patients with common varied immunodeficiency

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies, OKT3 and Pan T2, to induce interleukin-2 (IL2) production and proliferation in peripheral blood lymphocytes (PBL) from 14 patients with combined varied immunodeficiency (CVI). The median values of endogenous IL2 produced by mitogen-stimulated PBL was significantly lower in patients than controls irrespective of the mitogen used. The patients, taken as a group, had a significantly decreasedin vitro PBL response to mitogen stimulation when compared to controls. With the addition of a highly purified human IL2 preparation, the proliferative response in the majority of patients was significantly improved with all mitogens. Three patient groups could be distinguished: Group A (3/14) had full restoration of proliferative response with the addition of IL2, Group B (5/14) had partial restoration, and Group C (6/14) had no significant response. The monoclonal antibody, Pan T2, recognized a T-cell proliferative defect in 5 of 14 patients which neither PHA nor OKT3 recognized. This was not significantly corrected by the addition of IL2. This T-cell proliferative defect correlated with the lack of B-cell proliferation and immunoglobulin production in response to B-cell mitogens in three-fourths of the patients assayed. These data show that CVI patients are a heterogeneous group but have in common a decreasedin vitro production of IL2 resulting in a proliferative defect which is correctable at least in part,in vitro, in the majority by the addition of purified IL2.     

Detection by ELISA of IgA and IgM antibodies in secretion and IgM antibodies in serum in primary lower respiratory syncytial virus infection

Twenty-six infants and children with primary lower RS virus infection, diagnosed by the detection of RS virus in nasopharyngeal secretion (NPS) by use of immunofluorescent antibody (FA) technique, were studied with respect to the presence of IgA and IgM antibodies. Samples of NPS and serum obtained during the first 3-4 months following the beginning of illness, were investigated. Employing a reverse ELISA technique, we found IgM antibodies in the acute, but not during the convalescent, phase of illness in NPS from 20 of the patients and in serum from 21 of the patients. The majority of the IgM antibody conversions observed occurred in NPS as well as in serum on days 5-8 following the illness. RS virus IgA antibodies, also detected by a reverse ELISA technique, were demonstrated in NPS in 22 of the patients, with antibody conversions being found in 19 of the patients on days 5-8 following the beginning of the illness. Two patients still had IgA antibodies in NPS approximately 3 months FSOI. By comparison, RS virus was detected in acute-phase NPS by double-antibody sandwich ELISA in 25 of the 26 patients investigated.     

Determination of human IgG and IgM class antibodies to West Nile virus by enzyme linked immunosorbent assay (ELISA)

An enzyme-linked immunosorbent assay (ELISA) was developed and used for the detection of IgG and IgM antibodies to West Nile virus in human sera. Thirteen paired sera of clinical cases and 24 control sera taken randomly from a blood bank repository were tested. The sera were reacted in microtiter plates coated with PEG-treated WNV antigen. IgG or IgM antibodies were quantitated by the use of alkaline-phosphatase-conjugated anti-human IgG or IgM antibodies. Of the 24 randomly collected serum samples, 7 were positive in the IgG-ELISA test. One positive by the IgM-ELISA was found to contain rheumatoid factor. In 12 of 13 paired sera of clinical cases, IgM as well as IgG antibodies were detected in the second serum sample taken about 3 wk after the onset of clinical signs. The IgM positive sera were screened for rheumatoid factor (RF) on IgG-coated plates. None of them contained RF. Antibody titers obtained by ELISA showed a good correlation with titers obtained by hemagglutination inhibition, complement fixation, and neutralization tests. The ELISA tests for detection of IgM and IgG antibodies to WNV therefore can replace the other serological methods for epidemiological surveillance and diagnostic purposes.     

The significance of blood levels of IgM,IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients

We developed an ELISA test using leishmania antigenic extracts to detect antigen-specific antibody responses, including subclass and isotype analysis, in visceral leishmaniasis (VL) patients from the Sudan. A total of 92 parasitologically proven patients were compared with cutaneous leishmaniasis, schistosomiasis, malaria, onchocerciasis and tuberculosis patients, as well as with healthy endemic and non-endemic controls. Some VL patients were examined before and after chemotherapy. VL patients showed significantly higher IgG responses compared with all other groups (93·4% sensitivity, 93·7% specificity), and higher (but not significantly) IgM responses. All groups showed low IgA levels. All groups showed low IgA levels. All IgG subclasses, IgG1, 2, 3, and 4, showed higher levels in patients than all other groups, with IgG1 and IgG3 levels being significantly reduced following treatment. The rank order for specificity and sensitivity for IgG subclasses was IgG3 > IgG I> IgG2> IgG4.     

Leukocyte migration inhibitory factor production by activated lymphocytes representing immunological memory or virus-receptor interaction: response of T cell subsets to Epstein-Barr virus nuclear antigen, response of B cells to UV inactivated Epstein-Barr virus

Both T and B lymphocytes are known to produce leukocyte migration inhibitory factor (LIF) after appropriate activation. We showed that EBV nuclear antigen (EBNA) triggered T cells for LIF production in an immunologically specific way: only T cells of seropositive individuals responded. Both Fc receptor positive and negative T cells produced LIF, and the presence of macrophages was necessary. The virus itself activated B cells independently of the serological status of the donors, thus the function was not based on immunological memory. This phenomenon was independent of the transforming capacity of the virus, because UV-inactivated virus also elicited LIF production by B lymphocytes. This triggering seems to be the consequence of the virus-receptor interaction on the cell surface.     

Reverse radioimmunoassays of IgM and IgG antibodies to Coxsackie B viruses in patients with acute myopericarditis

A reverse radioimmunoassay (RIA) of antibodies to enteroviruses, previously developed for the detection of IgM antibodies to Coxsackie B1 (CB1) and B3 (CB3) and to Echo 11 (E11) and 30 (E30) viruses, was extended in the present study for the detection of IgM antibodies to Coxsackie B2 (CB2), B4 (CB4), and B5 (CB5) viruses and of IgG antibodies to CB1-CB5, E11, and E30 viruses. After standardisation of the assays and application to a collection of serum specimens from patients with proven enterovirus infections, specimens from patients with diagnosed or suspected acute myo- and/or pericarditis (myopericarditis group), and control specimens from patients with nonenterovirus infections, were studied, as well as from apparently healthy subjects. Of the patients with enterovirus infections, 29 of 30 (97%) were positive in the IgM RIA and 19 of 25 (76%) in the IgG RIA. In the myopericarditis group, 18 of 37 (49%) patients showed Coxsackie B (CB) virus-specific IgM titres and 9 of 37 (24%) CB virus-specific IgG titres. In the control specimens very few positive responses were detected. The RIAs appeared to be type specific or at least predominantly type specific, provided that the amount of labeled virus was carefully standardised. The sensitivity of the RIAs seemed to be rather high for IgM but low for IgG. In the neutralisation (NT) test no significant rise or fall in titre against CB viruses was demonstrated in the myopericarditis group. It is concluded that the reverse IgM RIA may be valuable for studies of the role of CB viruses in acute myo- and/or pericarditis.     

Immature B cells in fetal development and immunodeficiency: studies of IgM, IgG, IgA and IgD production in vitro using Epstein-Barr virus activation

Epstein-Barr virus has been used as a B cell mitogen to explore the parallels between the B cells found in patients with hypogammaglobulinemia and the immature B cells in fetal tissues. Peripheral blood lymphocytes from 29 cases of late onset hypogammaglobulinemia (common variable immunodeficiency) and from 10 cases of X-linked hypogammaglobulinemia were depleted of T lymphocytes and stimulated with virus in vitro. Immunoglobulin production was measured over a 4-week culture period using inhibition radioimmunoassays for IgM, IgG, IgA and IgD. The results were compared with those seen with fetal liver cells, cord blood lymphocytes and adult lymphocytes. Virus-stimulated cells from fetal sources produced small amounts of IgG and IgA relative to IgM, the ratio of IgM to IgG in the second week being in all cases greater than 10. Similar patterns were seen in 25/29 cases of late onset hypogammaglobulinemia, and in the eight cases of X-linked hypogammaglobulinemia that responded in vitro. In contrast, the ratio of IgM to IgG was always less than 8 in cultures of normal adult peripheral blood or bone marrow lymphocytes, and also in cultures from four cases of hypogammaglobulinemia known independently to have abnormal circulating suppressor cells. Eight cases of selective IgA deficiency showed reduced IgA production; six of these showed a normal ratio of IgM to IgG production. Thus, the B lymphocytes which circulate in many patients with hypogammaglobulinemia are functionally immature.     

Preparation and evaluation of a recombinant Rift Valley fever virus N protein for the detection of IgG and IgM antibodies in humans and animals by indirect ELISA

This paper describes the cloning, sequencing and bacterial expression of the N protein of the Rift Valley fever virus (RVFV) ZIM688/78 isolate and its evaluation in indirect ELISAs (I-ELISA) for the detection of IgM and IgG antibodies in human and sheep sera. Sera used for the evaluation were from 106 laboratory workers immunised with an inactivated RVF vaccine, 16 RVF patients, 168 serial bleeds from 8 sheep experimentally infected with wild type RVFV and 210 serial bleeds from 10 sheep vaccinated with the live attenuated Smithburn RVFV strain. All human and animal sera that tested positive in the virus neutralisation test were also positive in the IgG I-ELISA. There was a high correlation (R² = 0.8571) between virus neutralising titres and IgG I-ELISA readings in human vaccinees. In experimentally infected sheep IgG antibodies were detected from day 4 to 5 post-infection onwards and IgM antibodies from day 3 to 4. The IgG I-ELISA was more sensitive than virus neutralisation and haemagglutination-inhibition tests in detecting the early immune response in experimentally infected sheep. The I-ELISAs demonstrated that the IgG and IgM response to the Smithburn vaccine strain was slower and the levels of antibodies induced markedly lower than to wild type RVFV infection.     

Significance of specific Epstein-Barr virus IgA and elevated IgG antibodies to viral capsid antigens in nasopharyngeal carcinoma patients

The feasibility of using elevated Epstein-Barr virus (EBV) specific-IgG antiviral capsid antigen (VCA) and IgA anti-VCA antibody levels as an aid in diagnosis of nasopharyngeal carcinoma (NPC) was analyzed by determination of serum antibody titers to EBV in 54 NPC patients, 114 healthy blood donors, and 40 family members by the immunoperoxidase assay (IPA). No significant difference was found in the prevalence rate of EBV IgG anti-VCA antibodies (titer greater than or equal to 20) between the patient group and the control and family groups (100% vs 92% and 90%, respectively). The prevalence rate of elevated EBV IgG anti-VCA titers (greater than or equal to 80, greater than or equal to 160, greater than or equal to 320, greater than or equal to 640) was significantly higher in the NPC patients than in controls. For example, at an IgG titer of greater than or equal to 320, the prevalence rate was 82% in the NPC patient group and 1.7% in the controls (P less than 0.0001). The prevalence of EBV IgA anti-VCA antibodies (greater than or equal to 10) was significantly higher in the NPC patients than in control and family groups (82% vs 6.1% and 0%, respectively). The prevalence rate for elevated EBV IgA anti-VCA (greater than or equal to 20) was found to be significantly higher (P less than 0.0001) in NPC patients than in the control group (70% vs. 1.7%). A significantly high proportion (P = 0.0004) of NPC patients who had serum EBV IgA anti-VCA titers of less than 20 had elevated IgG titers to VCA greater than or equal to 320 (21% vs 1.7% among controls). It appears that testing for IgG antibodies at a serum dilution of 1:320 and for IgA antibodies at a dilution of 1:20 by the IPA technique comprises the best combination for the differentiation between NPC patients and health controls (91% vs 3.4%), and it is suggested that these be used as screening markers for NPC patients.     

Diagnosis and follow-up of genital chlamydial infection by direct methods and by detection of serum IgG, IgA and secretory IgA

Purpose: To determine the prevalence of Chlamydia trachomatis infection in a high-risk population by direct and indirect methods and to evaluate the diagnosis of secretory immunoglobulin A (sIgA). Patients and Methods: Urethral or endocervical specimens from 78 patients (48 females and 30 males) were examined by cell culture, direct fluorescence assay, PCR Cobas Amplicor (Roche Molecular Diagnostics), and sIgA was detected by the recombinant lipopolysaccharide (LPS)-enzyme-linked immunoassay (rELISA). Serum from each patient was also obtained and analysed for the presence of IgG and IgA antibody by in-house microimmunofluorescence (MIF) and by the rELISA method (Medac, Hamburg, Germany). Results: The overall C. trachomatis prevalence determined by direct methods was 28%. The detection of sIgA antibodies was significantly higher in the group of patients with a positive direct detection (50%) than in the group of negative direct detection (10.7%). The Chlamydia-specific IgA antibodies were detected by the rELISA in 40.9 and 53.6% of group I (positive direct detection) and group II patients (negative direct detection), respectively. The species-specific IgA antibodies were detected by the MIF method in 18.2 and 16.1% of group I and II patients, respectively. Chlamydia genus-specific IgG antibodies were detected by the rELISA in 86.4 and 83.9% of group I and group II patients and, C. trachomatis specific IgG were present in 81.8 and 73.2% of group I and group II patients, respectively, as assessed by the MIF test. Conclusion: Combining the positive direct methods and/or positive sIgA antibody results from cervical or urethral specimens had an indication of current C. trachomatis infection.     

Studies on the T cell dependence of natural IgM and IgG antibody repertoires in adult mice

The present experiments address the thymic dependence of IgM and IgG natural antibody repertoires in adult euthymic and athymic BALB/c mice, as well as in athymic animals reconstituted with a fixed number of syngeneic T cells. Within 3 weeks of the transfer of 10⁷ syngeneic splenic T lymphocytes to athymic mice, the T cell compartment is essentially reconstituted in the peritoneal cavity (up to 80% of the numbers in euthymic animals), but is only 10–20% of controls in the spleen and lymph nodes. Early after transfer, there is an increase in the numbers of activated B cells and of immunoglobulin-secreting cells in the spleen, and within 1–2 weeks, the serum concentrations of IgG₁ and IgG_2a are fully reconstituted to control levels (30–40-fold increased). Multiparametric analyses of serum IgM and IgG repertoires revealed that euthymic and athymic mice share essentially all natural antibody reactivities towards syngeneic extracts of liver and muscle. When tested at the same immunoglobulin concentrations, however, nude sera consistently show higher values of reactivity in all detectable bands. The transfer of 10⁷ splenic T cells into athymic mice results in a general decrease of serum IgM reactivities, some of which become undetectable, and in alterations of the serum IgG repertoire as early as 1 week, and for at least 4 weeks after transfer. T cell transfer, however, fails to restore the euthymic IgM and IgG repertoires within 4 weeks. The present observations demonstrate that, after limited T cell reconstitution of nude mice, there is a rapid and quantitatively important increase of serum IgG₁ and IgG_2a production; the serum IgM reactivity repertoire is qualitatively similar in euthymic and athymic animals, but is generally decreased by T cell activity; and the serum IgG repertoire, which is qualitatively similar in euthymic and athymic animals, is amplified by T cell activity and partially altered by T cell transfer into athymic animals. These results raise questions on the mechanisms of B cell activation and natural antibody repertoire selection in T cell-deficient adult individuals.     

An enzyme-linked immunosorbent assay (ELISA) for IgG and IgA antibodies to respiratory syncytial virus in low dilutions of secretions of human serum and secretions

An enzyme-linked immunosorbent assay (ELISA) has been developed for titration of IgG and IgA antibodies to respiratory syncytial (RS) virus in low dilutions of human serum, colostrum, and nasopharyngeal secretions. Previously the sensitivity of RS virus ELISA on such specimens has been limited by nonspecific absorption of antibody, particularly IgA, to crude antigen preparations. For IgG antibody estimation in infant sera, this unwanted binding was reduced to workable levels by increasing the serum, salt, and detergent concentration of the diluent. Residual nonspecific binding of IgA in colostra appeared mainly due to antigen lipids or to lipoproteins. This was markedly reduced by partitioning Triton X-100-treated infected cell lysate antigens in Arklone. Using the modified ELISA technique for anti-RS virus IgA, good correlations were found with unfixed cell membrane immunofluorescence (MIF) for colostra (r = 0.81, P less than 0.001) and nasal secretions from adult volunteers. In several samples nonspecific absorption of antibody precluded MIF assay, but did not affect the ELISA. Although there was an overall correlation between ELISA for anti-RS IgG antibody in sera, the complement fixation test (r = 0.75, P less than 0.001), and MIF test (r = 0.82, P less than 0.001), the sensitivity of ELISA for antibody responses in convalescent sera of infants from 3 months to 2 years was poor. Conversely, the sensitivity of ELISA for antibody in the sera of older children and for transplacentally acquired antibody in very young infants was higher than that for the other two tests. ELISA was thus less reliable than either CF or MIF for detecting antibody rises in paired infant sera, particularly where maternally acquired antibody remained in the acute serum. The reasons for this apparent disparity are discussed.     

基于2008分期标准的壮族鼻咽癌各期患者中EB病毒Zta/IgG等抗体阳性率的比较

探讨桂西地区壮族鼻咽癌患者EB病毒EBNA1/IgA、Zta/IgG及Rta/IgG抗体阳性率与鼻咽癌2008分期的关系。收集140例未经治疗的鼻咽癌患者的血清,用酶联免疫吸附法(ELISA)检测EBNA1/IgA、Zta/IgG及Rta/IgG抗体,按"2008分期法"进行分期,分别计算临床分期的各抗体阳性率并进行两两对比,进行统计学分析。鼻咽癌各临床分期组EB-NA1/IgA、Zta/IgG及Rta/IgG抗体阳性率均有统计学差异(P<0.05)。III期的各抗体阳性率明显低于IV期临床分期(P<0.05),Rta/IgG抗体有显著差异(P=0.001)。壮族鼻咽癌患者EB病毒EBNA1/IgA、Zta/IgG及Rta/IgG抗体阳性率与鼻咽癌临床分期有关。或许EBNA1/IgA、Zta/IgG及Rta/IgG抗体对于评估鼻咽癌临床分期有一定的参考价值。     

Performance of a novel test for IgM and IgG antibodies in subjects with culture-documented genital herpes simplex virus-1 or -2 infection

Novel tests (BioPlex) for herpes simplex virus-1 (HSV-1) and HSV-2 IgG were compared with HerpeSelect HSV-1 and HSV-2 ELISAs for type-specific IgG. The sensitivity and specificity of BioPlex HSV-1 IgG were 94% (84/89) and 96% (119/124), respectively, with unselected sera, while the sensitivity and specificity of BioPlex HSV-2 IgG were 92% (109/118) and 98% (95/97), respectively. BioPlex IgM was compared with Diamedix IgM against sera from patients with culture-documented genital herpes. The test results were concordant in 81% of sera from HSV-1 patients and in 90% of sera from HSV-2 patients. Use of BioPlex IgM in addition to BioPlex IgG tests increased HSV-2 seroconversion detection from 47% of subjects to 70%. Use of Diamedix IgM in addition to Focus IgG ELISA increased HSV-2 detection from 40% of subjects to 70%. IgM was detected by BioPlex in 63% of sera from patients with early HSV-2 infection (< 30 days) and in 59% of sera by Diamedix. IgM was also detected in a large proportion of sera from subjects with established HSV-2 infection (33% by BioPlex and 29% by Diamedix). Addition of IgM testing substantially increased the ability to detect seroconversion early in infection. IgM is an indicator of recent infection only in subjects who lack detectable IgG.     

Reassessment of the impact of mucosal immunity in infection with the human immunodeficiency virus (HIV) and design of relevant vaccines

Conclusions The development of vaccines that would induce specific immune responses in the genital tract secretions would have far-reaching implications for not only the prevention of AIDS and sexually transmitted diseases but also the immunological control of fertility (4, 76, 88, 89, 123, 124, 149). Most of the currently studied vaccines utilize systemic routes of immunization which are of limited value for the prevention of mucosa-contracted diseases. The relative contribution of antigensensitized cells from PP or other inductive sites (e.g., rectal tonsils) to remote or adjacent effector sites (e.g., genital tract) as manifested by the appearance of corresponding S-IgA antibodies has not been studied extensively in humans despite its unquestionable practical importance. Exploration of immunization routes that are effective for induction of mucosal immune responses and that are based primarily on current knowledge of the origin of antibodies and of specific antibody-forming cells in mucosal tissues, together with novel antigen delivery systems (1, 76, 89, 130), is likely to reduce the incidence of many infectious diseases including AIDS and also reduce the cost of administration of such vaccines.