Viral antibodies in maternal and cord sera

Viral antibodies were determined in paired maternal and cord blood sera of 258 consecutive deliveries. Antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex type 1 (HSV-1), adenovirus (ADV), and varicella zoster (VZV) were tested by indirect immunofluorescence and to rubella (RUB) by hemagglutination inhibition. Analysis of the overall pattern of differences between maternal and cord blood showed a highly significant difference for all six viruses. Analysis regarding individual viruses showed significantly higher titers to CMV and RUB in cord blood, a higher titer to VZV in maternal blood, and similar levels of antibodies to EBV, HSV-1, and ADV in maternal and cord blood. Infants with one or more risk indicators (weight < 3 kg, Apgar score 7, clinical jaundice, meconium-stained amniotic fluid, respiratory distress syndrome) were defined as at risk. Infants free of such indicators were defined as normal. Significantly lower antibody levels to all six viruses were found in both maternal and cord blood of the at risk as compared to the normal group, while the ratios between the maternal and cord blood levels remained similar. Birth defects were found to have no effect on antibody titers. These results indicate an efficient and selective transfer through the placenta of certain viral antibodies and the possible association of lower antibody production with the presence of risk indicators in the infants.     

Loss of maternal measles antibodies acquired by vaccination against measles]

The objective of the investigation was to assess whether children of mothers who acquired measles antibodies resp. immunity by vaccination are at least for the first six months of their life protected by maternal antibodies. A group of fifty pregnant women mean age 18 years incl. their umbilical blood and blood of their children, mostly 5-6 months after birth, were examined by the haemagglutination inhibition and immunoenzymatic test. The levels of measles antibodies were detected in 11 women immunized against measles in cca 1970 and in 26 revaccinated women mostly after 5 to 11 years. In once vaccinated mothers and their umbilical bloods the mean HI titres were 1:8.5 and 1:14 resp. and the mean EIA titres were 1:3600 and 1:3040 resp. As to the eight newborn children at the age of 5 and 6 months 6 children did not have any protective antibodies. In twice vaccinated women and their umbilical bloods the mean HI titre was 1:10 and 1:16.4 resp. and EIA titres were 1:2937 and 1:3784 resp. Of the 15 newborn infants at the age of 4 to 6 months 11 infants did not have any protective antibodies. In 8 mothers without vaccination records and their umbilical bloods the mean HI titre was 1:7.5 and 1:25.5 and mean EIA titres were 1:8229 and 1:7360 resp. In none of their children at the age of 6 months measles antibodies were found. The finding of the lack of protection in children older than 6 months stimulates further research of the problem.     

The secretion of virus-neutralizing antibodies

Summary Considerable evidence supports the concept that the immune defense against infectious agents that attack primarily the cells of the mucosal linings lies in secreted antibodies belonging to the IgA class of immunoglobulins. The problem that thus arises, in connection with the possible use of adjuvants in active immunization against these infectious agents, is that of the relationships between antibodies in the serum and those in the secretions.We have performed experiments that show that passive transfer of IgA antibodies to the secretions takes place much more readily if the IgA molecules are already conjugated with an additional polypeptide chain that is normally attached to them in the secreting glands, and that has been called the transport piece. Our data provide direct evidence for an effective role of the said piece in the transport of IgA antibodies across the secreting glands.It appears likely that, under normal conditions, a high local concentration of IgA antibodies, that is the consequence of the presence of IgA plasma cells in the immediate proximity of the secreting epithelial cells, facilitates the conjugation of the IgA molecules with the transport piece; in fact we could show, by immunofluorescence, a prevalence of IgA plasma cells at the level of the mucosal linings of the respiratory tract.It would appear that factors (so far poorly understood) that increment the production of IgA antibodies at the mucosal and glandular levels might be of more practical importance than those that only raise the serum antibody levels with regard to the active immunity against the above mentioned infectious agents.This work was supported by a grant (DA-91-591-EUC-3638) of the United States Army European Research Office.     

Measles antibodies in nasal secretions and sera of children with measles.

Measles antibodies were determined, in the course of measles, in sera and nasal secretions of 54 and 27 children, respectively. The examinations were performed on the 3rd or 4th day (1st period) and between the 10th and 14th day (2nd period) after onset of rash in both sera and nasal secretions and after 25 to 60 days (3rd period) in sera only. Geometric mean titres of antibodies in sera determined by haemmagglutination inhibition (HI) and neutralization tests in the 1st period were 126.3 and 115.3 respectively. For the 2nd period the respective figures were 318.4 and 396.1 and for the 3rd period--388.0 and 445.6. Fractionation on Sephadex G-200 of sera from the 1st period revealed HI and neutralizaing antibodies associated mainly with the IgM serum globulin class. Measles HI and neutralizing antibodies were also found in nasal secretions of all 27 children, but their titres were much lower than in serum. The antibodies determined by indirect immunofluorescence in nasal secretions were associated with IgA in 26 and with IgG immunoglobulin in 15 of the 27 subjects. No IgM antibodies were found.     

Monoclonal antibody-based competitive enzyme-linked immunosorbent assay for detecting and quantifying West Nile virus-neutralizing antibodies in horse sera

A rapid immunoassay for detecting and quantifying West Nile virus (WNV)-neutralizing antibodies in sera was developed as an alternative to the plaque reduction neutralization test (PRNT), the gold standard test for WNV. The assay is a competitive, enzyme-linked immunosorbent assay using neutralizing monoclonal antibody 5E8 (NT-ELISA). A cutoff percent inhibition (PI) value of 35% (mean PI plus 3 standard deviations), with a specificity of 99%, was established based on analysis of 246 serum samples from horses free of WNV. The NT-ELISA detected neutralizing antibodies in all sera collected 7 or 14 days postinoculation from mice (n = 11) infected with lineage I (strain NY385-99) or II (strain B956) WNV. When sera from WNV-vaccinated horses (n = 212) were tested by NT-ELISA and PRNT, the NT-ELISA gave a positive result for 96.1% (173/180) of the PRNT-positive sera and 3.1% (1/32) of the PRNT-negative sera. Discrepancies between the two tests were observed mainly with sera with low PRNT(90) titers (expressed as the reciprocal of the highest dilution yielding > or = 90% reduction in the number of plaques) for WNV or low PIs by NT-ELISA. The overall agreement (k value) between the two tests was 0.86. A good correlation (r(2) = 0.77) was also observed between the tests for endpoint titration of sera (n = 116). In conclusion, the newly developed NT-ELISA may be a good alternative serologic assay for detecting WNV that can be used for large-scale testing of WNV-neutralizing antibodies in multiple species.     

Leukaemia-associated antigens in man. Detection by antibodies in maternal sera

A membrane antigen on peripheral blood lymphocytes from cases of chronic lymphatic leukaemia (CLL) is described. The antigen was detected by complement-dependent cytotoxicity using serum from a healthy pregnant woman, and appeared to be absent from the normal lymphocyte population in these patients. The serum was also cytotoxic for some acute leukaemia blast cells and for cultured Burkitt lymphoma cells; absorption studies suggested that the CLL antigen is identical to the acute leukaemic antigen.

Similar antibody activity was also found in a number of HL-A typing antisera and could be separated from the HL-A specificity by absorption.

Although these antibodies are probably directed against foetal antigens, the leukaemic antigen could not be demonstrated on foetal tissues.

     

Foot-and-mouth disease virus-neutralizing antibodies induced in mice by anti-idiotypic antibodies.

A neutralizing monoclonal antibody (nmAb) to foot-and-mouth disease virus (FMDV) was used as antibody-1 (AB1) to induce anti-idiotypic antibodies (a-IdAb) in rabbits. The rabbit a-IdAb (AB2) were isolated on protein A-Sepharose, followed by cycles of separation on idiotype and isotype affinity columns. The specificity of the AB2 for the paratope of AB1 was determined by direct binding to AB1 in solid-phase radioimmunoassay (SP-RIA), and by competition RIA (C-RIA) with virus for binding to the AB1. The AB2, termed a-2PD11, was utilized to immunize six groups of female Swiss mice at weekly intervals with either one of three formulations, in doses of 50 micrograms or 5 micrograms, given in single subcutaneous (s.c.) spots. Anti-viral antibody (AB3) was first detected by RIA at the fifth week in the 50 micrograms/dose groups, and maximum levels were reached at the sixth week in the 50 and 5 micrograms/dose groups. The AB3 levels were at least three times higher for mice given 50 micrograms doses. In addition, the AB3 were also shown to neutralize FMDV infectivity in tissue culture and in a suckling mouse protection assay. Overall, mice exhibited variable responses to immunization with AB2. In a subsequent trial, mice received multispot s.c. and footpad injections of 50 micrograms of a-2PD11 coupled to keyhole limpet haemocyanin (KLH) on a weekly basis. In these mice, AB3 was detected earlier than in mice immunized with single s.c. injections. These results support the use of a-IdAb as potential surrogates of critical determinants for FMD vaccines.     

Molecular characterization of measles virus circulating in the Indian Ocean Islands during 2005-2006 and in France in 2006

Despite the availability of safe and immunogenic vaccines, measles still causes significant morbidity and mortality especially in Africa. In this study, two measles outbreaks in the Indian Ocean Islands; Mayotte in 2005-2006 and Seychelles in 2006 were studied. Nasopharyngeal swabs, urine and/or blood samples were collected from patients with clinically diagnosed measles. Measles viruses were isolated in four cases from patients in Mayotte. Measles strains circulating in both outbreaks were determined to be genotype D4 when compared to the WHO reference strains. During this time, measles virus was isolated from patients in France and they were also found to belong to the same genotype. The viruses clustered into two distinct D4 subgroups; The Indian Ocean strains were similar to the Montreal-subgroup, whereas the French strains associated with the Johannesburg-subgroup. The Indian Ocean strains formed a homogeneous group. They shared four specific amino acids in the 3' region of the N gene and two amino acids in the H gene, which differed from other genotype D4 viruses. This suggests that the same measles lineage circulated in Mayotte and Seychelles. Sequence comparison of the French isolates with other measles strains showed that they were more closely related to strains circulating in Germany in 2005, which had their origin in Romania. This study provides the baseline for molecular epidemiology of measles virus in Mayotte and Seychelles. The knowledge of circulating measles virus will help in documenting measles elimination program. This report also highlights the fact that progress of measles elimination is blighted continually by the phenomenon of measles importation.     

Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses

To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses.     

The effects of maternal haemoglobin as an indicator of maternal nutritional status on,maternal measles antibodies of mother-infant pairs at birth

Background

Maternal measles antibodies (MMA) are actively transferred through the placenta from mother to foetus. A relationship could exist between MMA of mother-infant pairs and maternal nutritional indicator (haemoglobin).

Objectives

This study reviewed the effects of maternal haemoglobin (Hb) on MMA of mother-infant pairs at birth.

Methods

One hundred and fifty three mother-infant pairs were enrolled in this study using the systematic random sampling method. Means of maternal Hb and MMA of mother-infant pairs were compared using the Student t test. Correlation coefficients of maternal Hb and MMA of mother-infant pairs were also determined. Multivariate analysis of variable (MANOVA) and covariates (MANCOVA) was used to investigate the effects of maternal Hb (fixed factor), gestational age, maternal age, birth weight (covariates) on combined MMA of mother-infant pairs (dependent factors). Benferroni adjusted Univariate linear regression was used to investigate the dependent variables separately.

Results

There were 78 (51%) males and 75 (49%) females. The (mean ± SD) MMA of mother-infant pairs at birth were 134.66 ± 93.31 (95% CI, 119.76 – 149.56) U/ml, and 187.49 ± 85.01 (95% CI, 173.91 – 201.07) U/ml, and their correlation was significant (p = 0.025). Ninety one (59.5 %) mothers had low Hb, 62 (40.5 %) had acceptable Hb levels. The overall mean maternal Hb was 11.01 ± 1.00 (95% CI, 10.85 – 11.17) g/dl . A positive significant correlation was observed between maternal Hb and MMA of the newborn-infant (p = 0.031). The MANOVA showed a statistically significant difference between maternal Hb on the combined dependent variables (p =0.033); however, results for the dependent variables using the Benferroni adjusted Univariate analysis was significant for only MMA of the infants, (p = 0.009).

Conclusion

There was a significant association between aacceptable levels of maternal Hb and high MMA of the newborn-infants. Therefore, these newborn infants start out with higher MMA that could give them better protection against measles during infancy.     

DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate

To eradicate measles in developing nations a vaccine capable of being administered at birth may be necessary. We immunized newborn rhesus macaques with naked DNA encoding the measles virus hemagglutinin, fusion and nucleoprotein genes. Prior to vaccination we passively transferred measles immunoglobulin to mimic maternal antibody. In the presence or absence of measles immunoglobulin, 23 of 25 infant macaques had detectable cell mediated immunity and 16 had protective levels of neutralizing antibody. The co-administration of an IL-2/IgG plasmid augmented the vaccine, increasing cell mediated immunity in all infants and increasing the antibody response in infants vaccinated without immunoglobulin. We show for the first time that DNA vaccination can protect a newborn primate from the high-level viremia that correlates with severe measles, even in the presence of maternal antibody. Further, the addition of a molecular IL-2 adjuvant augments this DNA vaccine.     

Detection of group B streptococcal antibodies in human sera by radioimmunoassay: concentrations of type-specific antibodies in sera of adults and infants infected with group B streptococci.

Current interest in determining the possible protective role of antibodies against group B streptococcal disease prompted this study of the feasibility of using a radioimmunoassay to measure type-specific immunity in humans. The radioimmunoassay was standardized as a quantitative test for antibodies against the carbohydrate (CHO) antigens of all five group B types. The data showed that the CHO antigens extracted by a cold trichloroacetic acid-sonification method measure more antibodies than do the corresponding CHO antigens extracted by hot hydrochloric acid; that the Ia CHOs extracted from two different types, Ia and Ic, measure the same quantity of Ia antibodies; and that human sera contain antibodies reactive with all five type-specific CHOs. No evidence of "protective" antibody was found in the serum samples studied, although there was evidence of and antibody response in adults to prolonged colonization by group B streptococci. The wide ranges of antibody concentration in a serum bank collection, the broad reactivity of all human sera tested, and the mixed populations of antibodies in human sera that react with different determinants on the same type-specific CHO antigen (type III) indicate that further studies must be done to better define normal and susceptible populations and to determine antigenic components important in protection.     

Decay of passively acquired maternal antibodies against measles, mumps, and rubella viruses.

The decay of maternally derived antibodies to measles, mumps, and rubella viruses in Swiss infants was studied in order to determine the optimal time for vaccination. A total of 500 serum or plasma samples from infants up to 2 years of age were tested by enzyme-linked immunosorbent assay and fluorescent-antibody testing. The decline of antibody prevalence was slowest against the measles virus. By 9 to 12 months of age, only 5 of 58 (8.6%; 95% CI, 2.9 to 19.0) infants were antibody positive for the measles virus, and only 2 had levels above 200 mIU/ml. Mumps and rubella virus antibody seropositivity was lowest at 9 to 12 months of age with 3 of 58 (5. 2%; 95% CI, 1.1 to 14.4) infants and at 12 to 15 months with 1 of 48 (2.1%; 95% CI, 0.1 to 11.1) infants, respectively. Concentrations of passively acquired antibodies decreased rapidly within the first 6 months of life. We observed no significant differences in antibody prevalence or concentration according to gender in any age group. In conclusion, MMR vaccination at 12 instead of 15 months of age could reduce the pool of susceptible subjects in infancy and support the efforts to eliminate these infections, particularly in combination with a second vaccine dose before school entry.     

Anti-cholesterol antibodies in human sera

In the last 30 years many research showed that high serum cholesterol level is a great risk for the atherosclerosis. In recent years, it has become clear that the immune system has a major role in atherosclerosis development and progression, and has binding capacity to cholesterol as well. It has been demonstrated in animal experiments, that anti-cholesterol antibodies (ACHA) can prevent cholesterol diet induced atherosclerosis. Our group is looking for the answer, whether ACHA have the same function in animals and in humans, or not. In this review we summarize our studies in human sera. We measured serum ACHA levels in different groups of patients with atherosclerotic diseases in patients with viral infections and in healthy population. In the summary we write about the possible functions of ACHA in the human immune system.     

Anti-hapten antibodies in normal sera

Many normal human, rabbit and reindeer sera were found to inactivate bacteriophages coupled with synthetic haptens NIP (4-hydroxy-3-iodo-5-nitrophenylacetic acid), NP (hydroxy-3-nitrophenylacetic acid), DNP (2,4-dinitrophenol), oxazolone (2-phenyl-4-ethoxy methylene oxazolone) or penicillin G. Evidence was produced indicating that these inactivators are antibodies with specificities roughly as strict as those of early immune antibodies. While most of the phage-inactivation power was due to 19 S antibodies, 7 S inactivators with chromatographic characteristics of IgG were demonstrated. There were great inter-individual differences in various anti-hapten titers. In spite of that, inter-species differences could also be demonstrated.     

Heterophile antibodies in Nigerian sera

A heterophile agglutinin was found at a titre of 1:4 or greater in 332 of 336 Nigerian sera investigated. The antibody was demonstrated to be an IgM macroglobulin. Although many of the sera tested had high IgM levels, only a slight correlation was found between titres of heterophile agglutinin and IgM levels. Absorption studies differentiated the Nigerian heterophile agglutinin from the antibodies seen in glandular fever and serum sickness. No correlation was found between the occurrence of high titres of heterophile agglutinin and infection with malaria, onchocerciasis, loaisis or schistosomiasis. None of the subjects investigated was known to have trypanosomiasis, a parasitic infection in which heterophile antibodies are known to occur.     

Heterophile antibodies in pathologic human sera resembling antibodies stimulated by foreign species sera.

Studies were performed on heterphile antibodies originally described by Hanganutziu and Deicher and referred to as H-D antibodies. It was confirmed that these antibodies appear as a result of injections of foreign species sera. They differ from Forssman antibodies by combining with bovine erythrocytes and from Paul-Bunnell antibodies by reacting with guinea-pig kidney. it was demonstrated that H-D antibodies react in double diffusion gel precipitation tests with: (1) crude extract of bovine erythrocyte stromata; (2) purified fraction of this extract devoid of Paul-Bunnell antigen; (3) whole bovine serum and sera of several other species; and (4) thermostable ethanol-insoluble freactions of serum and organs of oxen and several other species. These various antigenic preparations gave usually reactions of complete or partial identity with each other. In several instances, two or even three precipitation lines could be detected. H-D negative human erythrocytes became coated with H-D antigen upon simple incubation with H-D-positive sera. H-D antibodies were also detected in some pathological human sera without any indication that the patients had ever received injections of foreign species sera. Such antibodies were undistinguishable from H-D antibodies engendered by injections of foreign sera.