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Biomedical subjects

R M Chanock

Publications and source records attributed to R M Chanock.

At least 181 records · Page 10Linked to original sources
PubMed1979

Temperature-sensitive mutants of influenza A virus: evaluation of the A/Victoria/75-ts-1A2 temperature-sensitive recombinant virus in seronegative adult volunteers.

An influenza A virus recombinant bearing the surface antigens of the A/Victoria/3/75 (H3N2) strain and the two ts genes of the A/Udorn/72-ts-1A2 virus was evaluated for attenuation, antigenicity, and protective effect in 42 doubly seronegative adult volunteers (i.e., individuals who lacked detectable serum antibodies for the hemagglutinin and neuraminidase antigens). This recombinant, which had a 37 degrees C shutoff temperature for plaque formation and ts mutations on the genes thought to code for the P1 and P3 polymerase proteins, infected 90% of the volunteers. Of the volunteers, 5% developed mild coryza or rhinitis but other signs or symptoms were not observed, indicating that the A/Victoria/75-ts-1A2 recombinant was more attenuated than the A/Victoria/75-ts-1[E] recombinant. Vaccinees shed virus for a shorter interval and at a lower titer than did the A/Victoria/75-ts-1[E] vaccinees. Each ts-1A2 isolate retained the ts phenotype indicating that the recombinant was stable genetically in doubly seronegative adults. Finally, the ts-1A2 recombinant induced significant resistance to subsequent challenge with A/Victoria/75 wild-type virus.

Adult↗
PubMed1979

Cold-adapted variants of influenza A virus: evaluation in adult seronegative volunteers of A/Scotland/840/74 and A/Victoria/3/75 cold-adapted recombinants derived from the cold-adapted A/Ann Arbor/6/60 strain.

Influenza A/Scotland/74 (H3N2) and A/Victoria/75 (H3N2) cold-adapted (ca) recombinant viruses, prepared by mating the A/Ann Arbor/6/60 (H2N2) ca donor virus and influenza A wild-type virus, were evaluated in adult seronegative volunteers (serum hemagglutination-inhibiting antibody titer, </=1:8) for level of attenuation, antigenicity, and genetic stability of the temperature-sensitive and ca phenotypes. At 10(7.0) to 10(7.5) 50% tissue culture infective doses the A/Scotland/74 and A/Victoria/75 ca recombinant viruses were clearly attenuated and antigenic. However, one of eight vaccinees infected with 10(7.5) 50% tissue culture infective doses of the A/Scotland/74 ca recombinant had a febrile reaction (39 degrees C). At a 10-fold higher dose (10(8.5) 50% tissue culture infective doses), 4 of 12 A/Scotland/74 vaccinees had a febrile and/or systemic reaction. Febrile reactions were not observed in volunteers who received the A/Victoria/75 ca recombinant virus, whereas 3 of the 12 vaccinees had mild upper respiratory tract symptoms, in one instance associated with mild systemic manifestations. Significantly, the serum hemagglutination- and neuraminidase-inhibiting antibody responses were comparable to those induced by wild-type virus. Both ca recombinant viruses were shed in low titer for a short period of time. Each isolate retained the temperature-sensitive phenotype. However, there was evidence of genetic instability of the ca marker in that 7 of 24 isolates exhibited some loss of the ca property, and one isolate completely lost the capacity to produce plaques at 25 degrees C. The retention of a low level of residual reactogenicity in the A/Scotland/74 ca recombinant suggests that acquisition of the ca and temperature-sensitive phenotypes by a ca recombinant virus may not always bring about a satisfactory level of attenuation for individuals lacking hemagglutinin immunity.

Adaptation, Physiological↗
PubMed1979

Intramuscular inoculation of live respiratory syncytial virus induces immunity in cotton rats.

Intramuscular inoculation of infant or weanling cotton rats with 10(2.2) to 10(4) plaque-forming units of respiratory syncytial virus induced significant or complete resistance to infection in both the upper and lower portions of the respiratory tract. This resistance did not appear to be the result of in vitro neutralization of virus during homogenization of tissue. Virus was not recovered from the local site of inoculation after 5 min and was never detected in the respiratory tract of intramuscularly inoculated rats. Attempts to detect viral antigens at the site of inoculation by using indirect immunofluorescence were unsuccessful. However, inactivation of infectivity of three different strains of respiratory syncytial virus markedly reduced or completely ablated antigenicity and protective efficacy by the intramuscular route. This suggests that these viruses underwent limited replication, perhaps restricted to an abortive cycle, at the local site of inoculation. An immunosuppressive effect of passive maternally derived immunity was observed. Only 50% of weanling rats possessing passive maternal serum antibody were successfully immunized by intramuscular vaccination with live virus.

Animals↗
PubMed1979

Prevalence of antibody to the Norwalk virus in various countries.

Serum samples from children and adults from several countries were tested by radioimmunoassay for antibody to the Norwalk virus. Antibody was commonly found in adults from all the countries tested. Antibody appears to be acquired more rapidly in children from underdeveloped countries than in children from the United States.

Adolescent↗
PubMed1979

Live Victoria/75-ts-1[E] influenza A virus vaccines in adult volunteers: role of hemagglutinin immunity in protection against illness and infection caused by influenza A virus.

To explore the relationship between neuraminidase immunity and the degree of attenuatíon of live influenza A virus vaccines, a comparative evaluation of three Victoria/75-ts-1[E] (Vic/75-ts-1[E]) recombinant viruses in serum hemagglutination-inhibiting-negative (titer, </=1:8) adult volunteers was performed. These three ts-1[E] viruses had a similar restriction of replication at 38 degrees C in vitro, and each possessed the two attenuating genes of the ts-1[E] donor strain (13). However, Vic/75-ts-1[E] recombinants 81 and 113 possessed both Vic/75 hemagglutinin (H3(75)) and Vic/75 neuraminidase (N2(75)), whereas Vic/75-ts-1[E] recombinant 67 had Vic/75 hemagglutinin but the N2(65) neuraminidase. Vic/75-ts-1[E] recombinant 67 was significantly more attenuated than Vic/75-ts-1[E] recombinants 81 and 113 in that fewer local and systemic signs and symptoms of illness were observed in those volunteers who received clone 67. These findings were consistent with our previous observations which suggested that the following two factors contribute to the attenuation of ts-1[E] vaccine strains in adults: (i) the attenuating effect of the two ts-1[E] genes and (ii) the neuraminidase immunity of the host. Vic/75-ts-1[E] recombinant clone 67 vaccinees developed an immunological response to the H3(75) hemagglutinin in the absence of a response to the N2(75) neuraminidase. To assess the role that anti-hemagglutinin immunity induced by an attenuated live virus vaccine plays in resistance to influenza A virus, vaccinees who received recombinant 67 were challenged with Vic/75 wild-type virus, and their responses were compared with those of Vic/75-ts-1[E] vaccinees who received recombinant 81 or 113. Each of the three groups of ts-1[E] vaccinees was significantly protected against illness induced by wild-type virus infection, although resistance was not complete. However, the clone 67 vaccinees were protected less against infection. The infection-permissive resistance induced by clone 67 resembled that previously described for inactivated neuraminidase-specific vaccines. These results suggested that a ts-1[E] recombinant that possessed the hemagglutinin of a new pandemic variant, the neuraminidase of the preceding subtype, and the two ts-1[E] ts genes would be satisfactorily attenuated for children and adults with neuraminidase immunity and could induce resistance to illness caused by the new pandemic wild-type influenza A virus.

Adolescent↗
PubMed1979

Relationship of genotype of recombinants of influenza A/Hong Kong/68-ts-1[E]virus used as live virus vaccines to virulence in humans.

Influenza A/Hong Kong/68-ts-1[E] virus is a temperature-sensitive mutant developed for use as a live virus vaccine (B. R. Murphy, E. G. Chalhub, S. R. Nusinoff, J. Kasel, and R. M. Chanock, J. Infect. Dis. 128:479--487, 1973). This virus and temperature-sensitive recombinants derived by mating it with A/Udorn/72, A/Georgia/74, or A/Victoria/75 wild-type virus have been administered to volunteers in clinical trials on the assumption that the ts-1[E] temperature-sensitive genetic lesions on a polymerase gene (P3) and on the nucleoprotein gene (NP) would determine a satisfactory and reproducible level of attentuation regardless of the genetic constitution of ts-1[E] recombinants at other loci (B. R. Murphy, D. D. Richman, S. B. Spring, and R. M. Chanock, Postgrad. Med. 52:381--388, 1976). In this paper, the parental origin of genes in the ts-1[E] recombinants was determined by using the technique of polyacrylamide gel electrophoresis of virion ribonucleic acid segments in the presence of a denaturing agent (urea). When tested in individuals who lacked immunity to hemagglutinin antigen, attenuation of the ts-1[E] recombinants appeared to correlate with inheritance of the ts-1[E] temperature-sensitive genes at the P3 and NP loci and with the level of preinfection neuraminidase immunity. There was no evidence that other genes from the ts-1[E] donor virus played a role in attenuation.

Genes, Viral↗
PubMed1979

Respiratory syncytial virus infection in inbred mice.

Respiratory syncytial virus infected the nose and lungs of each of 20 strains of inbred mice, with viral titers varying 100-fold from least permissive to most permissive strains. Viral titers appeared to be under genetic control, but did not correlate with the H-2 haplotype.

Animals↗
PubMed1979

Respiratory syncytial virus infection in owl monkeys: viral shedding, immunological response, and associated illness caused by wild-type virus and two temperature-sensitive mutants.

Intranasal inoculation of owl monkeys with wild-type respiratory syncytial virus induced upper respiratory tract disease in each of seven animals. The response of owl monkeys to two highly defective, temperature-sensitive, multiple-lesion mutants was then compared to the pattern seen with wild-type respiratory syncytial virus. These mutants, ts-1 NG-1 and ts-1 NG-16, were derived from the ts-1 mutant that had been remutagenized with nitrosoguanidine (NG). Previously the ts-1 NG-1 and ts-1 NG-16 mutants had been shown to be more temperature sensitive and more stable genetically than their ts-1 parent. Both ts-1 NG-1 and ts-1 NG-16 produced infection that was delayed in onsent compared to wild-type virus infection. However, the mutants were shed from the upper respiratory tract for the same period of time and at the same titer as wild-type virus. The serum neutralizing antibody response to infection with the mutants was nearly equivalent to that elicited by wild-type virus. However, the extent of disease induced by the mutants was significantly less than that seen with wild-type virus. These observations suggest that the mutants are potential vaccine condidates and should be subjected to additional in vivo testing in primates and, ultimately, humans.

Animals↗
PubMed1979

Enhancement of antigen incorporation and infectivity of cell cultures by human rotavirus.

Infection of cell cultures with human rotavirus preparations was attempted and the effects of trypsin and low-speed centrifugation on antigen incorporation, as demonstrated by immunofluorescence and radioimmunoassay, were determined. In addition, the effect of viral aggregation on antigen incorporation was investigated by filtering viral preparations. Four strains of human rotavirus were employed, and the results were compared to those obtained with two tissue culture-adapted animal rotaviruses. Centrifugation and trypsin appeared to have little or no effect on infectivity of the tissue culture-adapted (simian rotavirus) or -adaptable (Nebraska calf diarrhea virus) strains, whereas centrifugation and viral aggregation appeared to be essential for the human viruses. In addition, trypsin enhanced antigen incorporation of the human strains to some extent. Infectivity for cell cultures and in vitro human rotavirus protein formation was demonstrated by [35S]methionine incorporation, and the specificity of this human viral protein was established by radio-immunoprecipitation.

Animals↗
PubMed1979

Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children.

A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.

Child, Preschool↗
PubMed1978

Epidemiology of human rotavirus Types 1 and 2 as studied by enzyme-linked immunosorbent assay.

To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes.

Antibodies, Viral↗
PubMed1978

Enzyme-linked immunosorbent assay for identification of rotaviruses from different animal species.

Rotaviruses cause gastroenteritis in man and a wide variety of animal species. They cross-react in many immunologic tests and have a similar appearance by electron microscopy, making differentiation among them difficult. Rotaviruses derived from different host species were distinguished by postinfection serum blocking virus activity in an enzyme-linked immunosorbent assay (ELISA). Thirty-three rotavirus isolates from children living in three different parts of the world could not be differentiated by this technique, but they were distinct from four strains recovered from calves, and a series of strains isolated from piglets, foals, monkeys, and infant mice. The four bovine strains were similar, but they could be differentiated from the other animal strains, each of which exhibited a distinct pattern when tested by the ELISA blocking technique.

Animals↗