Heterotypic Antibody Research Articles

Characterization of Antibodies Produced in Natural and Experimental Coxsackievirus Infections

Summary Neutralizing, hemagglutination-inhibiting (HI), complement-fixing (CF) and precipitating coxsackievirus antibodies produced in natural infections of man and experimental infections of rhesus monkeys were characterized with respect to their sedimentation properties in sucrose density gradients and sensitivity to 2-mercaptoethanol (ME). Early appearing neutralizing and HI antibodies consisted largely of 19 S immunoglobulins; these were replaced by 7 S antibody globulins in convalescent-phase sera. Determining the ME sensitivity of neutralizing and HI antibodies in sera from human coxsackievirus infections did not give a particularly reliable indication of the current infecting virus type; in some instances homotypic antibody did not show significant reductions in titer after ME treatment, and in other instances heterotypic antibody was ME-sensitive to the same extent as homotypic antibody. Complement-fixing antibodies to the coxsackieviruses were invariably ME-resistant and demonstrable only in the 7 S immunoglobulin fraction, even in initial infections with a coxsackievirus. In both natural and experimental infections specific precipitating antibody was ME-sensitive and present in the 19 S immunoglobulin fraction, while group precipitating antibody was ME-resistant and present in the 7 S fraction.

Heterotypic Antibody Responses in Man Following Vaccination with Adenovirus Type 1 Hexon Antigen

Vaccination of 11 adult male volunteers with adenovirus type 1 hexon antigen resulted in the formation of heterotypic as well as homotypic serum neutralizing antibody responses. The relative frequency of responses to serotypes belonging to immunologic group 3, which includes type 1, was significantly higher than those which occurred to serotypes in group 1 or group 2.

Antibody Responses of Rhesus (Macaca Mulatta) Monkeys Experimentally Infected with Coxsackieviruses of Group B and Group A, Type 9

Summary Heterotypic antibody responses to the echoviruses, polioviruses and reovirus type 1 were studied in rhesus monkeys which had been infected via the oral route with group B or group A, type 9 coxsackieviruses. Second or third infections with a coxsackievirus were shown to elicit heterotypic antibody responses to certain of the echoviruses but not to the polioviruses or reovirus type 1. The greatest amount of heterotypic reactivity was seen in complement fixation tests, and a number of heterotypic echovirus antibody responses were demonstrated in gel diffusion tests. Significant increases in hemagglutination-inhibiting antibody were also seen to some of the echoviruses, and in a few instances these were associated with low and transient rises in neutralizing antibody. The coxsackievirus infections produced a diversity of echovirus antibody responses, and no patterns of immunologic relationships between the various coxsackievirus and echovirus types could be established.

Pneumococcal neuraminidase.

Lee, L. T. (Columbia University, New York, N.Y.), and C. Howe. Pneumoccal neuraminidase. J. Bacteriol. 91:1418-1426. 1966.-The elaboration of neuraminidase by pneumococci grown under optimal conditions in liquid medium was studied in relation to the bacterial growth cycle. The enzyme was found free in the culture medium in increasing concentration throughout most of the logarithmic phase of growth, at the end of which enzyme concentration had reached a maximum. Only a small fraction of the total neuraminidase was cell-associated at any time. It appears, therefore, that pneumococcal neuraminidase is actively secreted by dividing cells and does not accumulate solely as a result of cellular autolysis. Neuraminidase in cell-free extracts (types I, III, VII, and XIV) was neutralized both by homotypic and by heterotypic antibody, thus demonstrating it to be a group antigen. The enzyme was separable in agar gel electrophoresis from other protein and polysaccharide pneumococcal antigens. Limited immunochemical data suggest that pneumococcal neuraminidase may be of relatively low molecular weight.

An Immunologic Classification of Heterotypic Antibody Responses to Adenoviruses in Man

SummaryStudies of heterotypic antibody responses in volunteers infected or immunized with adenoviruses indicate the presence of 3 distinct immunologic groups of serotypes. These groups correspond to an earlier classification of adenoviruses by Rosen which was based on varying patterns of agglutination of rat and rhesus monkey erythrocytes. Review of published epidemiologic studies reveals a strong association of heterotypic antibody responses after natural illness with the classification described. Some interpretations of the role of this classification in the epidemiology of adenoviruses is offered and the possibility of a broadly effective vaccine prepared from serotypes representing the three immunologic groups is suggested.

Studies of Parainfluenza Viruses

Summary Homotypic and heterotypic antibody responses were demonstrated in rabbits, guinea pigs, hamsters, chickens and monkeys following immunization with DA or other parainfluenza viruses. The extent of heterotypic antibody responses was found to be dependent on the degree of susceptibility of a specific host to the virus used, and the presence or absence of preexisting parainfluenzal antibodies. Heterotypic rises were interpreted as recall reactions or anamnestic responses based upon previous experience with a specific virus in a susceptible host. Cross-protection among DA and other parainfluenza viruses could not be demonstrated in vivo. The distinct antigenic properties of DA virus illustrated the probable existence of a fifth parainfluenza virus type.

Heterotypic Hemagglutination-Inhibition Antibody Responses in Volunteers Inoculated with Adenovirus Types 26 and 27

Summary In a study of heterotypic HI antibody rises in two groups of volunteers inoculated with adenovirus types 26 and 27, respectively, a high frequency of reciprocal responses between the inoculating types was found and is interpreted as indicating an immunologic relationship between them. Similarly, a significantly elevated frequency of heterotypic responses to type 13 among volunteers inoculated with type 26 suggested a possible immunologic relationship between these types. There was a low percentage of heterotypic responses to 22 other adenovirus types. The presence of heterotypic HI antibody before inoculation was associated with a somewhat greater frequency of postinoculation heterotypic rises.

STRAIN SPECIFICITY OF TYPE 1 NEUTRALIZING ANTIBODIES DEVELOPING IN CHILDREN FED WITH TYPE 1 SABIN'S ATTENUATED VIRUS (LSC 2AB).

The following results were obtained in an investigation on strain specificity of type 1 antibodies in children fed with the LSc 2ab virus: a) All investigated sera possessed a definite degree of strain specificity; b) the degree of strain specificity of postinfection antibodies did not seem to depend on their titres; c) the presence of heterotypic antibodies did not influence the strain specificity of the type 1 antibodies.

A Comparison of the Reactivity of Polivirus Complement-Fixing Antigens (Native, Heated and Sucrose Density Gradient C and D) with Human Sera

Summary Acute- and convalescent-phase serum speciments from poliomyelitis patients were tested in parallel against crude untreated (native), crude heated and sucrose density gradient-purified C and D complement-fixing antigens of the three poliovirus types. The native antigens were somewhat superior to the D antigens for detecting the occurrence of diagnostically significant rises in antibody titer, but the homotypic and heterotypic antibody titers against both the native and D antigens showed fairly good correlation indicating that the native antigens produced in HeLa cells consisted largely of D antigen. Age and prior vaccination (Salk vaccine) exerted a similar influence on antibody titers to the native and D antigens in that older patients showed fewer significant increases in antibody level than did younger patients and vaccinated patients showed rises in antibody of lower magnitude than did nonvaccinated patients. Titers to the heated and C antigens were similar with the exception that type 3 heated antigen showed greater heterotypic activity than did type 3C antigen. For diagnostic purposes purified D antigens were not found to possess any advantages over crude native antigens that would warrant the extra time and manipulations involved in their preparation.

ETIOLOGY OF RESPIRATORY INFECTIONS

Sixty viruses were recovered from 58 of 114 infants and children ill of respiratory infections. Two outbreaks, one caused by RS and the other by influenza B viruses, occurred during the study period. RS and influenza B viruses totaled 55% of the virus yield. Other viruses recovered were parainfluenza types 1, 2 and 3 (14 strains), reovirus, type 1 (5 strains), adenovirus (5 strains), and mumps (1 strain). Two viruses were lost and remain unidentified. Good correlation was obtained between viruses and development of specific antibody. A small fraction of infants had dual virus infections; heterotypic antibody responses were observed in 20% of the patients. These were considered to represent in part successive infections with specific viruses. Fourteen of 18 RS viruses, 6 influenza, and all except one of the parainfluenza viruses (type 3) were associated with laryngotracheobronchitis, bronchiolitis, and pneumonia. None was associated with any single clinical category. RS was associated more often with pneumonia than bronchiolitis; influenza B was associated less often with these than with upper respiratory infection. Analysis of virus-positive and virus-negative subgroups for bacterial "pathogens" and leukocytosis indicated that pneumonia of virus-negative infants was very likely bacterial in origin. Evidence was also obtained of concurrent bacterial infection in a fraction of patients yielding viruses.

Heterotypic Antibody Response After Feeding of Monovalent Attenuated Live Poliovaccine

Heterotypic Antibody Response After Feeding of Monovalent Attenuated Live Poliovaccine

Heterotypic antibody response after feeding of monovalent attenuated live poliovaccine.

THE goal of vaccination against poliomyelitis is the production of enduring immunity by a single administration of vaccine. With killed vaccine of the presently available potency this is not possible. With live vaccine there are a number of reports1 2 3 4 5 6 showing conversions for two or three serotypes after a single feeding of trivalent vaccine. It has usually been assumed that such multiple conversions are indicative of multiple infections by the virus types in the vaccine. The extent to which such multiple conversions are due to heterotypic responses to infection by only a single type in the vaccine has not been adequately . . .

Hemagglutination-Inhibition Antibody Responses in Human Adenovirus Infections

SummaryPaired sera from 36 children naturally infected with adenovirus types 1, 2, 3, or 5 and from 27 adults naturally infected with adenovirus types 4 or 7 were studied for homotypic and heterotypic hem-agglutination-inhibition (HI) antibodies and for complement-fixing (CF) antibody. Homotypic HI responses were observed in most instances. Heterotypic HI responses were relatively uncommon among the children but occurred in adults with about the same frequency as has been reported for heterotypic neutralizing antibody responses in the same type of population. Significant CF antibody responses were detected in most of the adults but in less than one-half of the children.

Heterotypic Antibody Responses by Rabbits Inoculated with Poliovirus

Summary Rabbits were found to acquire neutralizing capacity for homotypic and heterotypic poliovirus and for ECHO 12 virus following inoculation with a single poliovirus type. The neutralizing capacity for heterotypic and heterologous viruses was shown to have properties of antibody, in that it was produced by antigenic stimulus, was demonstrated in heat-inactivated sera and was not dependent upon the cellular component of the antigen. Rabbits previously immunized with type 2 poliovirus were found to have an enhanced (anamnestic) response to the poliovirus type 1 and 3 components of trivalent vaccine when compared with the control, unsensitized rabbits. Such an anamnestic response was further evidence for the antigenic relationship of of the three poliovirus types.

Observations on the Neutralizing Antibody Response to Group B Coxsackie Viruses in Patients with Central Nervous System Disease

Summary Sera from 540 patients with central nervous system disease were examined by a colorimetric technique for neutralizing antibodies to group B, types 1–5, Coxsackie viruses. Diagnostically significant increases in homologous antibody titer were demonstrated in 50% of the 238 patients from whom a group B Coxsackie virus was isolated. The neutralization test permitted a laboratory diagnosis of 33 cases of group B Coxsackie virus infections from which it was impossible to isolate a viral agent. Increases in the level of heterotypic antibody were seen in only 10% of this group of 271 patients. Although high titers of neutralizing antibody to group B Coxsackie viruses were frequently seen in individuals with laboratory evidence of infection with other viral agents, 4-fold or greater rises in antibody to group B viruses were encountered in only 3 of 101 such patients.

The use of new antigens in the complement-fixation test for acute poliomyelitis

A complement-fixation test for acute poliomyelitis using unheated antigens derived from suckling mouse brain infected with poliovirus Type 1 or Type 2 is described.The results of tests in 62 patients clinically diagnosed as cases of acute poliomyelitis in a recent epidemic and in 26 controls are recorded.The CF tests were positive in 100% of 53 cases with poliovirus Type 1 and/or Type 2 in stool. A positive result was obtained in 23 (76%) of 30 cases whose sera were examined in the first 7 days of illness.Negative tests of the initial serum samples were found in 15 (28·5%) of 53 cases, but all these became positive in titres of 40 or 80 on testing of convalescent serum.In 31 (69%) of 45 cases whose sera were re-tested between the 3rd and 4th weeks of illness the CF antibody levels rose, reaching titres of 80 or 160 in most instances. Of the remaining 14 cases only one dropped in insignificant degree (from titre 320 to 160) and the 13 stationary results had been positive in titres of 40–160 on initial tests most of which were performed in the 2nd week of illness.Homotypic CF antibody response without crossing was found in 37 (71%) of 52 cases with Type 1 or Type 2 virus in stool. In the cases of crossing the heterotypic antibody response was either transient, diminishing or stationary in all and in only low titre in most instances.In 26 control cases there were seven positive CF tests, but one of these was nonspecific, five were in lowest titres, and one case appeared to have had recent poliomyelitis infection.Heating the antigens did not broaden the reaction. It caused only slight loss of potency except in two cases in which the CF titre increased substantially.The antigenic preparation described appears to be superior to antigens of other origin in the diagnosis of acute poliomyelitis by complement-fixation tests, as positive tests are recognized earlier in the illness and the titres are higher. Homotypic results were obtained in all cases and no instance of false negative occurred in this series.I would like to thank the medical staff of the Cape Town City Hospital for Infectious Diseases for the trouble taken in collecting stools and paired sera, and Prof. Kipps for his interest in this work. I am indebted to Miss Karin Larssen for valuable technical assistance.

Studies of the Significance of the Recall Phenomenon in the Antibody Response to Adenovirus Vaccine and Infection

Summary The antibody responses of military recruits following administration of type 4 or 7 adenovirus vaccine and of patients suffering infections with adenovirus type 4 or 14 were studied. Type 4 vaccine induced significant neutralizing antibody against type 4 virus, a slight increase in antibody against types 3 and 14, and no antibody against type 7. The antibody-producing capacity of type 7 vaccine was greater than that of type 4 vaccine. Type 7 vaccine produced a marked neutralizing antibody response to types 3, 7 and 14, and a slight increase in antibody against type 4 only. The response to types 4 and 7 vaccine as measured with the complement-fixation test was poor in comparison to the neutralizing antibody response and tended to be type-specific. An assay of neutralizing antibody in sera from recruits showed that antibody against types 3, 7 and 14 was common at the time of the vaccination study or previously, whereas antibody against type 4 was less prevalent. It appeared that increases in heterotypic neutralizing antibody occurred more frequently when heterotypic antibody was present in the prevaccination or preinfection serum at a level of 1:2 to 1:16 than when no antibody was found The findings are discussed and compared to those of other studies. The data support the concept that the heterotypic antibody response to adenovirus vaccination or infection is conditioned by the recall phenomenon.

AN ENDEMIOLOGICAL STUDY OF ENTERIC VIRUS INFECTIONS

An endemiological study of enteric viruses was conducted among 136 normal children, living in households in two socio-economic groups, over a 29 month period in Charleston, West Virginia. A repeatable seasonal incidence of enteric virus excretion was noted with over 90 per cent of isolations occurring in the months of June to October. Of 592 stools examined in District I, a lower socio-economic group, 8.3 per cent yielded virus as compared to 3.1 per cent of 966 stools examined in District IV, an upper middle class district with good environmental sanitation. Among the 77 viruses isolated in tissue cultures of monkey kidneys, 44 per cent were ECHO or orphan viruses, 37 per cent Coxsackie viruses, and 19 per cent poliomyelitis viruses. Among poliovirus carriers, and 15 family contacts, 10 individuals had simultaneous heterotypic and type-specific antibody responses. The heterotypic ones were usually present at low levels and were transient in nature. Family infection with certain orphan viruses was also evident from antibody development which occurred following isolation of virus in the sentinel child.

Antigenic Crossings within Poliovirus Types.

SummarySeventy poliovirus strains, identified as single types by their reactions in the neutralization test, were studied in the complement-fixation reaction. For each strain an antigen was prepared in monkey kidney culture and this was tested against three standardized sera, each representing a different type. About half of the newly isolated strains were found to be ditypic and showed Type 1 and 2, or Type 2 and 3, antigens. A few strains were tritypic. The major antigen identified in the complement-fixation test agreed with the type assigned to the strain from its reaction in the neutralization test. The findings may help to explain the heterotypic antibody response in poliomyelitis infection of man, and the epidemiological correlations between the prevalence of Type 2 antibodies and immunity to Type 1 or Type 3 strains.

ANTIBODY RESPONSES TO NATURALLY OCCURRING POLIOMYELITIS INFECTIONS IN CHILDREN

Thirteen of fourteen children with a clinical diagnosis of poliomyelitis showed high neutralizing antibody titers in tissue culture tests aganst prototype viruses, as early as two days after the first symptom, and persisting for as long as 18 months without significant change in titer. A significant increase in titer from that during the first week was occasionally encountered, but the initial titer was usually in the same range as that of the subsequent 18 months. The 14th child had antibodies against none of the prototype poliomyelitis viruses, though his clinical history was quite compatible with a non-paralytic infection. In the third month this patient's Type 2 antibody rose after six negative serums to 1:5120, possibly indicating an inapparent poliomyelitis infection several months after an erroneous diagnosis of poliomyelitis. Stool specimens were available from seven of the 14 children. Six Type 1 poliomyelitis viruses and one Type 2 virus were recovered from these stools. Neutralizing antibody titers against the patient's own virus closely paralled those against the homologous prototype virus. When differences did occur, they were in favor of higher antibody titers against the patient's own virus. Serums from 10 patients had antibodies against more than one prototype virus. With the exception of only two patients, antibodies against one of the prototype viruses were present far in excess of the others. Possible explanations for the heterotypic antibodies are discussed. Neutralization tests, as performed, appear to be of value in ruling out a diagnosis of poliomyelitis, but not in establishing the diagnosis.