Immunoglobulin class-specific antibody response in respiratory syncytial virus infection measured by enzyme immunoassay

Immunoglobulin class-specific enzyme immunoassay (EIA) was used for determination of antibody responses in sera collected from 26 children with acute primary respiratory syncytial virus (RSV) infections. All 26 patients had IgG antibody responses with a significant titer increase in 24 (92%); an IgM antibody response was detected in 19 of the 26 (73%). From patients aged 6 months or less only 5 of 8 produced detectable IgM antibodies, whereas all patients aged 1–2 years did so. IgM antibodies appeared within 1 week after onset of illness and persisted from 20 days to 2–3 months. An IgA antibody response was observed in 20 of 26 (77%) patients with a significant titer increase detected in 17 of 26 (65%) patients. In some patients the persistence of IgA antibodies followed that of the IgM antibodies, but in others the IgA antibody titers remained stable up to the end of the follow-up. The most sensitive assay system for serological diagnosis of acute RSV infection in children was the determination of titer increases by IgG antibody.     

Identifying infections with respiratory syncytial virus by using specific immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent assays with oral-fluid samples

Currently, respiratory syncytial virus (RSV) infection is identified in epidemiological studies by virus antigen or nucleic acid detection in combination with serology. Oral-fluid specimens may provide a noninvasive alternative to blood, and oral fluid is more suitable for sampling outside of the clinic setting. We evaluated an indirect enzyme-linked immunosorbent assay for the detection of RSV-specific immunoglobulin G (IgG) and IgA by using oral-fluid samples collected from individuals with RSV infections confirmed by an immunofluorescent antibody test. For five children sampled repeatedly from birth, antibody profiles in oral fluid quite consistently tracked those in paired sera, and RSV infections were detected by rising titers of antibodies of at least one Ig class. Specific IgG responses were generally more reliable than IgA responses, except in early infancy, where the reverse was sometimes true. For a further five young children from whom oral fluid was collected weekly following RSV infection, boosted antibody responses, frequently of a transient nature, lasting a few weeks, were observed; specific IgG responses were of longer duration and more pronounced than specific IgA responses. Our data show significant promise for the use of oral fluid alone in RSV infection surveillance. The observed rapid dynamics of the antibody responses are informative in defining study sampling intervals.     

RSV molecular characterization and specific antibody response in young children with acute lower respiratory infection.

The presence of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) were studied in 254 hospitalized Argentinean children with acute lower respiratory infection tract (ALRI). The specific humoral immune response and partial sequences of the G protein gene were studied in a subset of 22 children with RSV confirmed infection. The RSV IgM detection and the RSV IgG titration were made by immunofluorescence assay (IFA) in pairs of sera. The partial RSV G gene sequences were obtained by an RT-PCR amplification directly from de NPAs. RSV was present in 44.5% of the children. The RSV IgM was detected in 22.7 and 68.8% of the first and second sera, respectively. The IgG geometric mean titers of the acute and convalescent sera were 8 and 589. The RSV IgG titration was able to define 86.4% of the RSV confirmed cases. The percentage of coincidence between RSV IgM detection in the second sera and diagnosis by RSV IgG titration was 72.7% and no significant differences were observed. The nucleotide sequence of one group A and three group B viruses were identified. The first one was related with circulating viruses in Madrid, Montevideo and Mozambique during 1992, 1989 and 1999, respectively. The three sequences identified as group B viruses were closely related with circulating viruses in 1998 from South Africa and Canada during 1999 and 2000. The data obtained in our study provide the first approach at the molecular level (nucleotide) of the RSV circulating strains in Argentina and the lack of genotype patterns previously determined make necessary a continuous molecular surveillance in order to contribute to the understanding of the behavior of this virus in our community.     

Cell-free and cell-bound antibody in nasal secretions from infants with respiratory syncytial virus infection.

Twenty-two infants under 9 months of age hospitalized with bronchiolitis or pneumonia due to respiratory syncytial virus (RSV) were serially sampled to determine the pattern of secretory antibody response. Using double labeling techniques, we found several types of immunoglobulin in secretions: cell-free antibody to RSV of the immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) classes; and immunoglobulins of all three classes bound to RSV-infected cells shed from the nasal epithelium (presumably cell-bound antibody to RSV). IgA attached to RSV-infected epithelial cells was almost always detected in the first available nasal sample (day 1 or 2 of hospitalization). In contrast, cell-free anti-RSV IgA first appeared an average of 3.5 days later at a time when virus antigen was disappearing from the secretion. IgG and IgM attached to RSV-infected cells appeared more irregularly. The titer of cell-free anti-RSV IgM was often higher than that of IgA early in the illness and declined as the infection resolved. Cell-free anti-RSV IgG was usually present earlier than IgA and rose during convalescence.     

Monoclonal antibody-based capture enzyme immunoassays for specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to respiratory syncytial virus

Monoclonal antibodies (MAbs) to the fusion protein (F), attachment protein (G), and nucleoprotein (N) of respiratory syncytial (RS) virus were evaluated for use as detector antibodies in immunoglobulin G (IgG), IgA, and IgM capture enzyme immunoassays. MAb assays were tested against assays using polyclonal antibodies (PAbs) with serum specimens from patients with and without evidence of recent RS virus infection. Assays developed with N MAbs were comparable to or better than PAb assays for detecting specific IgG and IgM antibodies but were somewhat less sensitive for IgA. F MAb assays were less sensitive for IgG and IgM antibodies but identified specific IgA in some specimens negative by N MAb assay. G MAb assays were insensitive for IgG and IgM antibodies but did detect about 50% of the IgA antibodies identified by the PAb assay. The basis for the low sensitivity of the G MAb assays is unclear, since many of these specimens were positive for IgG antibodies to G by Western immunoblot. The sensitivity of MAb assays varied with patient age: N MAb assays detected specific antibody responses to RS virus in all immunoglobulin classes in both adults and infants less than 1 year of age, F MAb assays detected specific IgG responses in adults and IgA responses in both adults and infants, and G MAb assays only detected IgA responses in adults. A mixture of N and F MAbs was complementary overall, identifying 54 of 55 (IgG), 51 of 52 (IgA), and 16 of 17 (IgM) serum specimens positive by PAb assay. These MAb assays were also specific with specimens tested from persons without a history of recent RS virus infection. The availability of these MAb-based assays offers other laboratories the opportunity to have long-term, standardized reagents and tests for serological diagnosis of RS virus infection.     

Influenza virus serology--a comparative study

Virus isolation or influenza virus antigen detection are the most rapid tests for diagnosis in the acute stage of influenza virus infection. As serology is easier to carry out, the synthesis of serum IgM, IgA and IgG was studied in two well-defined patient groups, infected with influenza B virus (cohort 1, n = 37) and influenza A virus (cohort 2, n = 40), diagnosed by antigen detection and/or virus isolation within 36 h after onset of symptoms. IgM was found in 13 influenza B patients (35%), IgA in 12 patients (32%), whereas a significant antibody rise was found in 33 patients (92%) by enzyme-linked immunosorbent assay (ELISA) and 74% by haemagglutination inhibition assay (HAI). For the influenza A cohort these numbers were respectively 18 (45%), 27 (68%) and 24 (62%) HAI (72%). In age-matched controls, who were bled on the first day of illness of the enrolled patient low prevalence was found for IgA and IgG, for influenza B respectively in 2 and 18%, and for influenza A in 4 and 39%. Studying the kinetics of the antibody response, we found that virus specific IgA and the bulk of IgG is synthesised within the first week of the infection. It is concluded that the finding of a specific serum IgA is highly indicative of an acute influenza infection.     

Evaluation of monoclonal antibody-based capture enzyme immunoassays for detection of specific antibodies to measles virus.

Monoclonal antibodies to the hemagglutinin protein, fusion protein, phosphoprotein, matrix protein, and nucleoprotein of measles virus were evaluated as detector antibodies in capture enzyme immunoassays (EIAs) for the detection of specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to measles virus. A pool of monoclonal antibodies to hemagglutinin protein and nucleoprotein proved optimal and was further evaluated. Specific IgM was detected in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of clinical measles cases and vaccinees, in 26% of healthy persons, and in 36% of infants 8 months postvaccination; consequently, IgA antibodies were not a useful indicator of recent measles infection. A significant increase in IgG antibodies between paired specimens was detected in 92% of clinical cases and all vaccinees. Only 59% of infant specimens had persistent IgG antibodies as detected by capture EIA at 8 months postvaccination, whereas all specimens had antibodies as detected by hemagglutination inhibition and plaque neutralization. An alternative indirect EIA, in which antigen was directly absorbed to the solid phase, was more sensitive than the capture design, detecting IgG antibodies in all infants postvaccination. When standardized with a microneutralization assay for the detection of persistent antibodies, the indirect IgG EIA gave predictive values for positive and negative tests exceeding 90%. Our capture IgM and indirect IgG EIAs provide a practical combination of serologic tests for the determination of acute measles virus infection and past exposure to measles virus or vaccine, respectively.     

An epidemic of respiratory syncytial virus in elderly people: clinical and serological findings

In 1984-1985, an outbreak of respiratory syncytial virus (RSV) infection occurred in two geriatric wards. Among 68 patients (mean age +/- SD = 82.5 +/- 12.5 with respiratory signs, 52 had signs caused by RSV infection. Among all patients, the clinical and serological attack rates were 61.2% and 75.0%, respectively. The most frequent clinical presentation was intensive coughing (96.1%) and fever (96.1%) associated with expectorate (63.5%). The duration of the respiratory symptoms was 5 to 7 days. The disease gradually resolved, although in eight (15.4%) patients complications occurred. For periods of up to 1 year after infection, 172 sera were obtained and tested by complement fixation test (CFT), fluorescent assays for titrating specific IgG, IgA, and IgM, and Western blotting. Specific IgM appeared in six (11.5%) of the infected patients and peaked 2 to 6 months after infection, and there was no significant correlation with severity of clinical symptoms. However, higher peak G and A antibody responses were observed in persons with rales (CFT: P = 0.008; IgG: P = 0.042; IgA: P = 0.020), cough (IgG: P = 0.034), sputum (IgG: P = 0.030), dyspnea (CFT: P = 0.024), conjunctivitis (CFT: P = 0.025), and bronchitis (CFT: P = 0.018). The temporal patterns of IgA and CFT results were found to be similar, whereas IgG peaked later, i.e., between 2 and 6 months. The patients with the most severe symptoms had the highest antibody titers obtained by conventional tests and by Western blots. Thus, RSV can be an epidemic pathogen among elderly persons, although this illness is usually mild.     

Age related IgG subclass response to respiratory syncytial virus fusion protein in infected infants

Respiratory syncytial virus (RSV) fusion protein was purified by immunoaffinity chromatography using a mouse monoclonal antibody coupled to Affi-gel 10. The fusion protein was homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and free of other detectable viral or cellular protein. The purified fusion protein was used in a quantitative enzyme-linked immunosorbent assay (ELISA) to measure the age-related antibody response to this protein in infected infants. The four IgG subclasses, IgA and IgM levels were determined for infants under 6 months of age, infants aged 6 months to 1 year and infants aged 1 year and over. Most infants over 6 months of age showed marked increases in both IgG1 and IgG3 antibodies with poor or negligible response with IgG2 and IgG4. By contrast infants under 6 months failed to respond by the production of IgG antibodies, although increases in IgA and IgM levels were observed. These data may explain the failure of primary RSV infections to induce protective immunity and have implications for the strategic use of attenuated RSV vaccines.     

Comparison of five different immunoassays for the detection of Borrelia burgdorferi IgM and IgG antibodies

The performances of five commercially available enzyme immunoassays were compared for the detection of Borrelia burgdorferi IgM and IgG antibodies. Sensitivity was assessed with European serum samples collected from 45 patients with clinically defined Lyme disease in conjunction with a positive immunoblot (n = 44) or other serological test (n = 1). Sensitivities for the detection of IgM and IgG with each test were: Dako IgM 64%; Dako IgG 53%; Serion IgM 89%; and Serion IgG 88%. The Immunetics assay makes no distinction between IgM and IgG antibodies and had a sensitivity of 91%. Specificity was calculated by testing a control group comprising 40 patients with acute Epstein-Barr virus infection, cytomegalovirus infection, syphilis or rheumatoid factor positivity. The specificities achieved for each test were: Dako IgM 78%; Dako IgG 100%; Serion IgM 52%; Serion IgG 92%; and Immunetics 92%. The discriminatory power between control and patient samples appeared highest for the Immunetics assay. Between-run variation was comparable for the five tests and did not exceed 13%. When the Immunetics assay was used as an initial screening test, with low-titre positive results confirmed by an immunoblot, a sensitivity of 91% and a specificity of 100% were achieved. To attain maximal sensitivity, the Serion IgM and IgG tests were also performed on samples with negative Immunetics results. All positive Serion IgM and IgG results were also confirmed by immunoblot. In conclusion, the Immunetics assay, based on a synthetic C6 peptide, can be used reliably as an initial screening test for the serodiagnosis of Lyme disease.     

Tissue distribution of mucosal antibody-producing cells specific for respiratory syncytial virus in severe combined immune deficiency (SCID) mice engrafted with human tonsils.

Groups of C.B-17 SCID mice were reconstituted intraperitoneally with human tonsillar mononuclear cells (hu-TMC) from children seropositive for antibody to respiratory syncytial virus (RSV) and subsequently challenged intraperitoneally with inactivated RSV or sham-immunized. The synthesis and the distribution characteristics of human antibody to RSV in various murine tissues were studied using an enzyme-linked immunospot assay (ELISPOT). No specific antibody was observed in sham-immunized animals. In contrast, mice engrafted with hu-TMC exhibited the appearance of specific human antibody secreting cells (hu-ASC) after i.p. immunization with inactivated RSV. RSV-specific hu-ASC were detected only in animals engrafted with cells from donors seropositive for antibodies to Epstein-Barr virus. Hu-TMC engrafted mice showed RSV-specific IgM and, in lower numbers, IgG hu-ASC in several tissues including the lungs. Numbers of RSV-specific IgA hu-ASC were low, however, and detected only in the lung. No RSV-specific hu-ASC were detected in the intestine. These data demonstrate for the first time that hu-TMC-SCID chimeras respond to immunization with viral antigen. Furthermore, the results suggest that hu-TMC engraft in lungs but not in the intestinal tissue.     

Appearance of complement components and immunoglobulins on nasopharyngeal epithelial cells following naturally acquired infection with respiratory syncytial virus

Nasopharyngeal epithelial cells (NPEC) were collected from 144 infants and children with respiratory syncytial virus (RSV) infection, and were analyzed by fluorescent antibody techniques for the presence of cell-bound complement (C^/₃), IgA, IgC, and IgM class of immunoglobulins (Ig), and respiratory syncytial virus antigen. Viral antigen was present on the surface of NPEC in 100% of samples obtained in the first 3 days of illness. The percentage of patients positive for RSV antigen declined steadily, so that no patient still expressed viral antigen on NPEC by 57 days after the onset of illness. Cell-bound IgA, IgC, and IgM could be detected in most of the samples tested in the first 13 days after the onset of illness. Subsequently, the frequency of detection of cell-bound Ig gradually declined. Only 8–3 3 % of patients tested 57 days after the onset of illness expressed IgA, IgG, or IgM on NPEC. About 45% of samples tested in the first 8 weeks after the onset of illness exhibited complement binding to NPEC. The percentage of subjects showing cell-bound C^/₃ reached a maximum at 8–13 says after the onset of illness, while cell–bound C^/₃ could not be detected in any of the samples collected 57–90 days after the onset of illness. Although cell-bound C^/₃ was generally present in association with cell-bound Ig on NPEC, in a small percentage (4.6%) of patients cell-bound C^/₃ could be detected in the absence of any cell–bound Ig. Cell-bound C^/₃ and IgA, IgG, and IgM were present with equal frequency in patients with all forms of clinical disease caused by RSV, and in patients less than or greater than 6 months of age at the onset of illness.     

Identification of Aichi Virus Infection by Measurement of Immunoglobulin Responses in an Enzyme-Linked Immunosorbent Assay

Using inhibitory enzyme-linked immunosorbent assay, seroconversions to Aichi virus were detected in 24 (42.9%) of 56 patients with gastroenteritis in six outbreaks. Virus-specific immunoglobulin M (IgM) was detected in convalescent-phase sera from 7 of 24 patients. Of the other 17 patients, 12 developed a significant increase in both IgA and IgG levels and 5 developed a significant increase in IgG alone.     

Serodiagnosis of tuberculosis: comparison of immunoglobulin A (IgA) response to sulfolipid I with IgG and IgM responses to 2,3-diacyltrehalose, 2,3,6-triacyltrehalose,and cord factor antigens

Nonpeptidic antigens from the Mycobacterium tuberculosis cell wall are the focus of extensive studies to determine their potential role as protective antigens or serological markers of tuberculous disease. Regarding this latter role and using an enzyme-linked immunosorbent assay, we have made a comparative study of the immunoglobulin G (IgG), IgM, and IgA antibody responses to four trehalose-containing glycolipids purified from M. tuberculosis: diacyltrehaloses, triacyltrehaloses, cord factor, and sulfolipid I (SL-I). Sera from 92 tuberculosis patients (taken before starting antituberculosis treatment) and a wide group of control individuals (84 sera from healthy donors, including purified protein derivative-negative, -positive, healed, and vaccinated individuals, and 52 sera from nontuberculous pneumonia patients), all from Spain, were studied. The results indicated a significantly elevated IgG and IgA antibody response in tuberculosis patients, compared with controls, with all the antigens used. SL-I was the best antigen studied, showing test sensitivities and specificities for IgG of 81 and 77.6%, respectively, and of 66 and 87.5% for IgA. Using this antigen and combining IgA and IgG antibody detection, high test specificity was achieved (93.7%) with a sensitivity of 67.5%. Currently, it is widely accepted that it is not possible to achieve sensitivities above 80% in tuberculosis serodiagnosis when using one antigen alone. Thus, we conclude that SL-I, in combination with other antigenic molecules, could be a useful antigen for tuberculosis serodiagnosis.     

Detection of antibody to bovine syncytial virus and respiratory syncytial virus in bovine fetal serum.

Batches of commercial fetal bovine serum, described by the suppliers as antibody-free, all contained antibody to bovine syncytial virus (BSV) when tested by indirect immunofluorescence. Antibody to bovine respiratory syncytial virus (RSV) was not detected in these sera. Twenty-four percent of individual fetal bovine sera contained antibody to BSV, and 14% contained antibody to RSV when tested by indirect immunofluorescence. BSV antibody titers in fetal sera from dams with high BSV antibody levels were variable but always higher than RSV antibody titers. Radial immunodiffusion studies with BSV-positive sera revealed the presence of immunoglobulin M (IgM), IgG, and IgA, but the quantity of these immunoglobulins was not directly related to the BSV antibody titers. The evidence suggests that the antibody present in fetal sera arose as the result of infection rather than from maternal transfer across the placenta.     

Detection of respiratory syncytial virus in nasopharyngeal secretions by DNA-RNA hybridization.

We have developed an RNA-cDNA hybridization assay for the detection of respiratory syncytial virus (RSV) RNA in nasopharyngeal samples. We chose to use as probe a cDNA complementary to the nucleocapsid protein gene of RSV, integrated into the plasmid vector pBR322. The lower limit of sensitivity of the assay is 8.2 X 10(2) PFU of the Long strain of RSV. In throat washes with added cell-free virus, the assay can detect 3.3 X 10(3) PFU of RSV. Respiratory secretions were collected from a group of 104 infants in New Orleans, and 73 of the samples were tested for RSV by immunofluorescence (IF). All were then frozen at -70 degrees C for later testing by hybridization, and 67 were tested for RSV antigens by enzyme immunoassay (EIA). A second set of respiratory secretions from 48 infants in Denver were cultured for virus, assayed for RSV antigen by EIA, and then frozen for later testing by hybridization. For those samples on which IF was performed, hybridization, compared with IF, had a sensitivity of 49% and a specificity of 66%. For samples tested by EIA, hybridization had a sensitivity of 60% and a specificity of 81% compared with EIA. Compared with virus isolation, hybridization assay had a sensitivity of 73% and a specificity of 92%. With clinical samples, the sensitivity and specificity of the assay were improved with the addition of a control blot, which was hybridized to the plasmid vector (pBR322). The performance of the hybridization assay can be expected to improve when the assay is used with fresh clinical material rather than frozen samples.     

Performance of three microimmunofluorescence assays for detection of Chlamydia pneumoniae immunoglobulin M,G, and A antibodies

The microimmunofluorescence (MIF) test is considered the "gold standard" for laboratory diagnosis of acute and chronic Chlamydia pneumoniae infection. The performance of a MIF test based on C. pneumoniae antigen from Washington Research Foundation (WRF) was compared with those of assays from Labsystems (LAB) and MRL Diagnostics (MRL) by investigation of sera from three groups of patients: group I, 83 sera from 28 patients with atypical pneumonia; group II, 37 sera from 16 patients with acute C. pneumoniae or Chlamydia psittaci respiratory tract infection confirmed by PCR or culture; group III, 100 sera from 100 persons enrolled in the Copenhagen City Heart Study. The accordance among the results of the WRF assay and the two commercial assays was excellent for the immunoglobulin M (IgM) antibody detection rate (98%). The accordance in detection rates for IgG and IgA antibodies in sera from patients with acute infections was acceptable (87 and 88%), and in sera from group III, it was excellent (95 and 97%). The determinations of endpoint titers were reproducible with <1 dilution step difference for all three methods, except that the mean IgM antibody titer found by the LAB assay was almost 2 dilution steps higher than that found by the other two methods. Although the three assays use different C. pneumoniae strains as antigens, the detection rates and IgG and IgA endpoint titers were similar. The difference in endpoint titers of IgM antibodies is of no major concern, as the diagnosis of acute C. pneumoniae infection rests on the presence of IgM antibodies, not on their level.     

Detection of specific antibodies to severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein for serodiagnosis of SARS coronavirus pneumonia

We report the evaluation of recombinant severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) nucleocapsid protein enzyme-linked immunosorbent assay (ELISA)-based antibody tests for serodiagnosis of SARS-CoV pneumonia and compare the sensitivities and specificities of this ELISA for detection of immunoglobulin G (IgG), IgM, IgA, and their combinations with serum samples from 149 healthy blood donors who donated blood 3 years ago as controls and 106 SARS-CoV pneumonia patients in Hong Kong. The specificities of the ELISA for IgG, IgM, and IgA detection were 95.3, 96.6, and 96.6%, respectively, with corresponding sensitivities of 94.3, 59.4, and 60.4%, respectively. The present ELISA appears to be a sensitive test for serodiagnosis of SARS-CoV pneumonia, is much more economical and less labor-intensive than the indirect immunofluorescence assay, and does not require cultivation of SARS-CoV.     

The immunostimulating complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses

ISCOM is an efficient mucosal delivery system for RSV envelope proteins as measured by antibody responses in respiratory tract secretions and in sera of mice following two intranasal (i.n.) administrations. Intranasally administered RSV ISCOMs induced high levels of IgA antibodies both in the upper respiratory tract and in the lungs. In the lungs, a prominent and long-lasting IgA response was recorded, which still persisted 22 weeks after the second i.n. immunization when the experiment ended. Subcutaneous (s.c.) immunization only induced low IgA titres in the upper respiratory tract and no measurable response to RSV was found in the lungs. Differences were also noticed in serum between the i.n. and s.c. modes of immunization. ISCOMs given intranasally induced earlier, higher and longer lasting IgM and IgG1 serum anti-RSV antibody responses than those induced by the s.c. mode of administration. A low serum IgE response was only detectable at 2 weeks after i.n. immunization with ISCOMs and after s.c. immunization with an inactivated virus, but no IgE response was detectable after s.c. injection of ISCOMs. The serum IgA response was more pronounced following s.c. injection of inactivated virus than after i.n. application of ISCOMs, and a clear-cut booster effect was obtained with a second immunization. Virtually no serum IgA response was detected after the s.c. administration of ISCOMs. In conclusion, the high immune responses induced by RSV ISCOMs in the respiratory tract and serum after i.n. administration indicate prominent mucosal delivery and adjuvant properties of the ISCOMs, warranting further studies.     

Respiratory syncytial virus group-specific antibody response in nasopharyngeal secretions from infants and children after primary infection.

Respiratory syncytial virus (RSV) group-specific immunoglobulin A (IgA) and IgG enzyme-linked immunosorbent assay antibody and neutralizing antibody responses were determined for nasopharyngeal secretions (NPS) from 27 infants and children (6 to 18 months of age) undergoing primary infection with RSV group A or B strain. IgA and IgG antibody responses against RSV envelope glycoproteins (fusion [F] and large [G] glycoprotein) in NPS were also analyzed. Most subjects examined developed moderate levels of NPS IgA and IgG antibodies and neutralizing antibody activity to both group A and B strains in convalescent phase; however, the levels of antibodies to homologous strains were significantly higher than to the heterologous strains. Patients infected with group A developed antibodies in both F and G glycoproteins of A2 strains (group A). Patients infected with group B developed levels of antibody activity to F glycoprotein of A2 strain similar to those of patients infected with group A. However, these subjects developed little or no antibody response to G glycoprotein of A2 strain. These data suggest that the IgA and IgG antibody responses to G glycoprotein in the respiratory tract are group specific. It is suggested that lack of antibody response to the G glycoprotein of the heterologous group in the respiratory tract may determine the outcome of reinfection with other RSV strains.