NT Antibody Research Articles

Reactivity of human coronavirus OC43 and neonatal calf diarrhoea coronavirus membrane-associated antigens.

Human embryonic lung fibroblast cultures and Vero cell cultures infected with cell culture-adapted strains of human coronavirus (HCV) OC43 or neonatal calf diarrhoea coronavirus (NCDCV) were shown to possess highly cross-reactive membrane-associated antigens (MAA) by the indirect fluorescent antibody technique (IFAMA). MAA appeared 3 h post-infection, concurrently with the appearance of cytoplasmic antigens. Electron microscopic observations of cell cultures infected with either coronavirus strain and labelled with the immunoperoxidase antibody (IPA) technique for MAA detection showed that MAA consisted mainly of a strongly labelled, discontinuous, brush-like layer of amorphous material, strictly associated with the infected cell membrane. By light microscopy, reactivity of MAA with homologous and heterologous immune serum was similar to that of antigens detected by IPA in ethanol-fixed infected cells. IPA and IFAMA, but not haemagglutination-inhibiting (HI) and neutralizing (Nt) antibody, were strongly decreased by absorption of immune sera with trypsin-treated glutaraldehyde-fixed cell cultures infected with homologous virus. MAA IgG antibodies were detected by IFAMA in both human and animal sera. Sera from infants showing an HI and Nt, but not an IPA, antibody response to HCV OC43 were also free of detectable IFAMA antibody to HCV OC43.

RA27/3 rubella vaccine. A four-year follow-up.

RA27/3 rubella vaccine was given to 418 subjects aged 1 to 17 years in 1974, 201 of whom participated in a four-year follow-up study. Two vaccine-associated complications were reported. A 5-year-old boy had transient arthritis of the hip, and a 1-year-old boy had a pigmented macule at the inoculation site. Rubella reinfection was uncommon, occurring at most in three of our subjects. All of the 186 susceptible children seroconverted, and 182 had hemagglutination-inhibiting (HI) titers of 8 or greater at four-year follow-up (geometric mean titer, 30.3). In the four children whose HI titers declined to undetectable levels, both HI and neutralizing (Nt) antibodies had developed immediately postimmunization, and two had Nt titers at follow-up despite loss of HI antibodies. RA27/3 vaccine boosted HI titers in 15 seropositive subjects, but titers returned to preimmunization levels four years later. We concluded that RA27/3 vaccine produced durable immunity with very low rates of rubella reinfection and secondary vaccine failure during the four years since immunization.

Studies on rubella. II. Rubella antibodies in the cerebrospinal fluid with rubella meningoencephalitis (author's transl)

There have been a few reports of finding specific viral antibody in cerebrospinalfluid (C. S. F.) with rubella meningoencephalitis.C. S. F. from twelve patients with rubella meningoencephalitis were examinied forantibody to rubella by following techniques:Hemagglutination inhibition (HI) antibody determination was done using the standard microtitration technique. C. S. F. was not pretreated with kaolin to remove non-specific inhibitors because there was insufficient protein in C. S. F. to saturate the kaolin, and thus the range of dilution could be satarted with undiluted specimens.Neutralization test (NT) antibody was titrated employing plaque count method.Complement fixation (CF) antibody was examined with common microtitration technique.The results are as follows:1. Rubella HI antibody was found in the C.S.F. of all twelve patients. The HI antibody titer ranged from 1: 2 to 1: 128. The peak antibody level showed in acute phase and it decreased slowly depending on the day of illness. This pattern was opposite to the serum antibody pattern.2. Rubella NT antibody was found in the C.S.F. of six out of ten patients. The NT antibody titer ranged from 1: 2 to 1: 32. The NT antibody pattern depended on the day of illness and was similar to HI pattern.3. Rubella CF antibody was found in the C.S.F. of four out of ten patients. The CF antibody titer ranged from 1: 2 to 1: 8. The CF antibody pattern was similar to the NT pattern.4. An average serum/C. S. F. antibody ratio was as follows.First ten days after the onset, it was 65 for HI and 60 for NT. Ten to fifteen days after the onset, it was 153 for HI and 384 for NT and after sixteen days, 523 for HI and 768 for NT.5. No antibodies were found in the C.S.F. of the nineteen controls who had negative serum rubella HI antibody. In the case of another control group with all positive HI's in the serum, 16/19 (HI), 15/16 (NT) and 12/13 (CF) had negative titers. The positive cases were a mycoplasma encephalitis, a bacterial meningitis, an aseptic meningitis and an acute leukemia. The maximum antibody level of these cases was 1: 4.6. These results confirmed that rubella antibody could be found in the C.S.F. of the rubella meningoencephalitis and it could be diagnosed rapidly to determined the HI antibody titers in the C. S. F. It was also suggested that the rubella virus which was probably in the central nervous system could be neutralized by the antibody in the C. S. F.The further studies are required to clarify if these antibodies were produced in the central nervous systems or their localization there is due to a leak of the serum antibody through a hyperpermeable blood-brain-barrier.

Histocompatibility Types and Viral Antibodies

Serum neutralizing (Nt) antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and histocompatibility (HL-A) types, were determined in multiple sclerosis (MS) patients and in control subjects. Titers of Nt antibodies to HSV-1 and to HSV-2 were increased among subjects bearing HL-A3 or HL-A7 or both, whether they suffered from MS or not. The increases were statistically significant in the MS group. The MS and control groups did not differ significantly in levels of HSV-1 or HSV-2 Nt antibodies.

VIROLOGIC CONSIDERATIONS ON ANTI-DENGUE VACCINE

Possibilities of developing an anti-dengue vaccine are discussed based on our experimental findings with a dengue virus type 1 (DEN-1) Mochizuki strain. The Mochizuki strain virus was attenuated for human beings in the course of several passages through mouse brains since its isolation from the blood of a dengue patient in the 1943 epidemic in Nagasaki, Japan. This attenuated virus in the living state induced no abnormal symptoms after injection into human volunteers or monkeys, yet it stimulated production of specific anti-DEN-1 NT and HI antibodies and induced a prophylactic effect on the human beings against virulent dengue viruses (in the form of patient's serum) given experimentally. The immunogenic effects of the virus was maintained after passages in primary monkey kidney tissue cultures. Using the tissue culture virus, together with the 17D yellow fever (YF) vaccine, a combined immunization of human beings against DEN and YF was possible; production of the antibodies of significant titers against both viruses was unequivocally demonstrated. The partially purified virus was similarly effective in stimulating production of the anti-DEN antibodies, and the same statements could be made as to the viral components obtained by sucrose density gradient centrifugation. The virus was shown to multiply in the WI-38 cell line cultures, and this suggests application of this cell line to produce a live tissue culture vaccine.Conclusions of this review are : (1) the Mochizuki virus is completely attenuated; (2) yet it stimulates production of specific anti-DEN antibodies and induces protection against DEN-1 infection by virulent human virus; and (3) that possibility of developing a live tissue culture vaccine is suggested; this also makes possible a combined DEN-YF vaccination on the experimental basis. It is stated in the connection that the purified virus or its components can be used for the above purposes.Problems regarding the implication of “hypersensitivity hypothesis” of dengue and dengue hemorrhagic fever-shock syndrome in anti-DEN vaccination are in addition discussed.

Neutralizing antibodies to poliovirus and mumps virus in amyotrophic lateral sclerosis

Neutralizing (Nt) antibodies to poliovirus types 1, 2 and 3, and to mumps virus, were measured in sera from 27 patients with amyotrophic lateral sclerosis, and from 28 age- and sex-matched controls. No significant differences were observed in distribution or in geometric mean titers of antibodies, when the two groups were compared.

Complement-fixing and virus-neutralizing antibodies in cytomegalovirus infection as measured against homologous and heterologous antigen.

The serological response to infection with cytomegalovirus has been studied in five patients using heterologous and homologous antigens prepared from a laboratory strain—Ad 169—and a cytomegalovirus strain isolated from each patient, respectively. The study confirmed previous observations that the rise in CF antibodies precedes the rise in NT antibodies, especially in primary infections, and that the rise in NT titre runs over a longer course than the rise in CF titre. This more prolonged rise in NT titre can be utilized in the serodiagnosis of CMV infection in patients already having high CF titre in the first blood specimen taken. No differences between the CF antigen from the five newly isolated strains and the Ad 169 CF antigen were seen. Using the NT test it was found that one of the strains differed antigenically from strain Ad 169. This strain and strain Ad 169 seem, however, to be relatively closely related as it was possible in paired sera from the patient yielding the strain to demonstrate a parallel rise in NT antibodies with antigens prepared from each of them.

Complement-Fixing and Neutralizing Antibodies against Cytomegalovirus Strain AD 169 in Sera from Infants with Cytomegalovirus Infection

The serologic response to cytomegalovirus infection was studied in 20 children being infected during the first year of life. It appeared that the response in young children—as in adults—was characterized by a rapid rise in CF and NT antibodies, often resulting in high titers. Formation of CF antibodies appears to preceed formation of NT antibodies. Later in the infection, even though most children still had viruria, a decrease in both types of antibodies was seen, sometimes to very low levels. The tests were performed with antigen, prepared from strain Ad 169. It appears that this strain, in this area, is well suited as antigen because of the uniformity in the serologic response seen in most cases.

Isolation of human enteroviruses from beagle dogs.

SummaryOne hundred and sixty-four isolations of Coxsackie viruses B1, B3, and B5 and ECHO virus 6 related if not identical to human viruses of the same types, were isolated from nose, throat, and rectal swabs collected from beagle dogs. Such isolations have not been previously reported except from the ECHO virus 6 which was again recovered. Six unidentified, apparently identical viruses were also isolated. Low NT antibody titers against Coxsackie virus B3 and B5 were present in some of the sera collected from the dogs. No titers were observed for Coxsackie virus B1, ECHO virus 6 or one of the unidentified viruses. There was no correlation between virus isolation and serum titers.

流行性耳下腺炎弱毒生ワクチンに関する研究

The virulent Towata strain of mumps virus was successfully passaged in the chorio allantoic cavity of developing chick embryos, and it was noticed that Towata strain was considerably attenuated after many passages (described in the first report). Attenuated Towata strain of various passage numbers was used in 4 field trials for children in 1967 by the inhalation method. Similar degree of antibody response was obtained in each trial, without any clinical manifestations due to the vaccination. Increase in NT antibody titer was 8 to 18 fold, and 80 per cent of seroconversion was observed in sero-negative cases. The rate of sero conversion of NT antibody was higher than that of HI antibody in paired sera. It was noticed that many children who had low antibody also showed antibody response. In inhalation trials with Enders strain adapted to the chorio allantoic cavity, antibody response almost similar to that of Towata strain was obtained.

Rubella immunity as correlated to age and history of overt disease.

Serum specimens from 161 pregnant women or newborn children and from 280 females of different age groups, obtained in the cities of Stockholm and Eskilstuna, Sweden, were tested for neutralizing antibody to rubella virus, some of them also for hemagglutination-inhibiting antibody. Lack of NT antibody in undiluted serum suggested susceptibility to rubella in 15–20% of women of child-bearing age. There was some correlation — most evident in the younger age groups — between reported history of overt rubella and presence of NT antibody. The distribution of serum titers, NT as well as HI, and the actual rarity of reports on remote attacks of the disease suggested that ignorance of childhood rubella was the prime reason for the poorer correlation in adults.

Survey for antibodies against arthropod-borne viruses in man and animals in Italy. I. Serologic status of human beings and animals in a central Italian region (Fondi).

Summary Sera from 205 apparently healthy residents in the region of Fondi (central Italy) were tested by hemagglutination-inhibition against 10 different arboviruses: two from group A, five from group B, Bunyamwera, and the Sicilian and Neapolitan strains of Phlebotomus fever. About 29% of the sera reacted with one or more antigens: 1.9% to TBE, 8.3% to WN, 20.5% to Sicilian Phlebotomus fever and 9.7% to Neapolitan Phlebotomus fever. Sera from 153 domestic and wild animals of various species (cattle, goats, sheep, chickens, rabbits, pigs, rats, and wild mice), collected in the same area, were examined by the HI test against the same 10 antigens. Twenty-four percent of bovine sera, 32% of goat sera, and one sheep serum reacted with WEE antigen. Seven percent of bovine sera and 44% of goat sera showed antibody for TBE antigen; WN antibodies were found in bovine, goat, rabbit, rat and wild-mice sera. Some of the human and animal HI-positive sera were further tested with the corresponding viruses by mouse-neutralization test. The presence of TBE neutralizing antibodies was confirmed in human and goat sera; WN and WEE neutralizing antibodies were not encountered, indicating perhaps the presence of viruses closely related; NT antibodies to Sicilian Phlebotomus fever were not detected.

ROLE OF INTERFERON AND PARTIAL IMMUNITY IN INFLUENZA VIRUS INFECTION OF MOUSE LUNG.

SummaryThe mechanism of recovery from infection with the PR8 strain of influenza virus in nonimmune mice and in mice partially immunized with formalin-inactivated PR8 vaccine, was investigated. The results demonstrated that in the lungs of immunized mice limitation of virus growth is mediated primarily by specific serum NT antibody. ITF was not detected in the lungs of the immunized group challenged with a sublethal dose of virus but was demonstrated in the lungs of control mice from day 3 through day 5. It was not detected on day 7 when NT antibody appeared in the serum. Pulmonary virus growth, as indicated by tests for infectious, lethal and HA virus, was maximal from day 2 to day 5 at which time ITF content reached a peak. Thereafter, virus titers remained at a high level though declining when ITF was no longer demonstrated. The time of maximum lung consolidation was subsequent to these events. Partially immunized mice survived a lethal challenge of 106 EID50 and ITF was detected in the lung on day 5, ...

The geographal distribution in Sweden of viruses belonging to the Russian spring-summer-louping ill group. I. Serological survey of antibodies in cow sera.

NT antibodies to LI virus were found in the sera of Swedish cows from many parts of the country although only exceptionally in the north. The prevalence of positive specimens increased markedly towards the southeast. This geographic distribution apparently fits well with the occurrence of ticks in the country. An analysis, now in progress, of RSSE-LI antibodies in human cases of meningoencephalomyelitis seems to indicate a closely similar distribution of the human RSSE infections. It is thus obvious that the screening of cow sera for LI antibodies provides reliable information as to endemic regions of RSSE-LI-like viruses. There was nothing to suggest that nonspecific reactions occurred or impaired the results; in fact the very uneven geographic distribution of positive specimens, of high as well as low titers, should argue for specificity of the reaction.