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Biomedical subjects

M L Clements

Publications and source records attributed to M L Clements.

At least 73 records · Page 4Linked to original sources
PubMed1989

The influence of HIV infection on antibody responses to a two-dose regimen of influenza vaccine.

We studied whether a two-dose regimen of inactivated influenza virus vaccine was more effective than a single dose in inducing protective hemagglutination-inhibition antibody responses in patients infected with human immunodeficiency virus (HIV). Participants included subjects with acquired immunodeficiency syndrome, subjects with acquired immunodeficiency syndrome-related complex, and HIV-seropositive individuals with either lymphadenopathy only or no symptoms. Control subjects were HIV-seronegative heterosexuals and HIV-seronegative homosexuals. Two doses of inactivated influenza vaccine containing 15 micrograms of the hemagglutinin of influenza A/Taiwan/1/86(H1N1), A/Leningrad/360/86(H3N2), and B/Ann Arbor/1/86 were administered intramuscularly in the deltoid region 1 month apart. The second dose of vaccine did not significantly increase the frequency or magnitude of antibody responses of either HIV-seropositive or HIV-seronegative subjects over that achieved by a single dose. The two-dose regimen induced a protective level (greater than or equal to 1:64) of hemagglutination-inhibition antibody to influenza A(H1N1) or (H3N2) virus less often in subjects with symptomatic HIV infection than in uninfected control subjects (39% vs 87% or 46% vs 97%, respectively). Our results suggest that a substantial proportion of individuals with symptomatic HIV infection might remain unprotected from influenza, even after immunization with a two-dose regimen.

AIDS-Related Complex↗
PubMed1989

Comparison of the virologic and immunologic responses of volunteers to live avian-human influenza A H3N2 reassortant virus vaccines derived from two different avian influenza virus donors.

We compared the abilities of the six internal RNA segments of two avian influenza viruses, A/Mallard/Alberta/88/76 (H3N8) and A/Mallard/NY/6750/78 (H2N2), to confer attenuation on wild-type human influenza A/Bethesda/1/85 (H3N2) virus in seronegative adult volunteers. Live avian-human influenza A reassortant virus vaccines derived from either avian virus parent were comparable in the following properties: safety, infectivity, immunogenicity, and genetic stability. Since the avian influenza A/Mallard/Alberta/76 virus offered no clear advantage as a donor virus, we will conduct our future evaluations on live influenza A virus reassortants derived from the more extensively characterized avian influenza A/Mallard/NY/78 virus.

Animals↗
PubMed1989

Systemic and local antibody responses in elderly subjects given live or inactivated influenza A virus vaccines.

Intranasal live attenuated cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant virus and parenteral inactivated influenza A/Taiwan/1/86 (H1N1) virus were given alone or in combination to 80 ambulatory elderly subjects. An enzyme-linked immunosorbent assay was used to measure hemagglutinin-specific (HA) antibodies in serum and nasal wash specimens collected before vaccination and 1 and 3 months later. Serum immunoglobulin G (IgG) and nasal wash IgA HA responses were elicited in 56 and 20%, respectively, of 25 inactivated-virus vaccinees and in 67 and 48%, respectively, of 27 recipients of both vaccines but in only 36 and 25%, respectively, of 28 vaccinees given live virus alone. Inactivated virus, administered alone or with live virus vaccine, induced higher titers of serum antibody than did the live virus alone. In contrast, nasal IgA HA antibody was elicited more often and in greater quantity by the vaccine combination than by either vaccine alone. Despite these differences, the peak titers of local antibody mounted by each group of vaccinees were similar. By 3 months postvaccination, serum IgG and nasal IgA HA antibody titers remained elevated above prevaccination levels in 50 and 17%, respectively, of the inactivated-virus vaccinees and in 46 and 23%, respectively, of recipients of both vaccines but in only 19 and 7%, respectively, of the live-virus and systemic antibodies, if vaccinees. The finding that live ca influenza A virus induced short-lived local and systemic antibodies, if confirmed, suggests that live virus vaccination may not be a suitable alternative or adjunct to inactivated virus vaccination for the elderly.

Aged↗
PubMed1989

Effect of nitrogen dioxide exposure on susceptibility to influenza A virus infection in healthy adults.

The effect of NO2 exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, double-blind trial conducted in an environmentally controlled research chamber over 3 yr. Healthy, nonsmoking, young adult volunteers who were seronegative to influenza A/Korea/82 (H3N2) virus were randomly assigned to breathe either filtered clean air (control group) or NO2 for 2 h/day for 3 consecutive days. The NO2 concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects immediately after the second exposure. Only one of the 152 volunteers had any symptoms; this person had a low grade fever. Pulmonary function measurements and nonspecific airway reactivity to methacholine were unchanged after NO2 exposure, virus infection, or both. Infection was determined by virus recovery, a fourfold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups were 12/21 (2 ppm NO2) versus 15/23 (clean air) in Year 1, 17/22 (3 ppm NO2) versus 15/21 (clean air) in Year 2, and 20/22 (2 ppm) and 20/22 (1 ppm) versus 15/21 (clean air) in Year 3. Each group exposed to 1 or 2 ppm NO2 in the last year became infected more often (91%) than did the control group (71%), but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

The influence of human immunodeficiency virus (HIV) infection on antibody responses to influenza vaccines.

STUDY OBJECTIVE: To ascertain whether subjects infected with human immunodeficiency virus (HIV) generally develop protective hemagglutination inhibition antibody responses to inactivated influenza vaccines. DESIGN: Prospective study of 104 persons before and after immunization. SETTING: Outpatient clinic and hospital ward. PATIENTS: Persons with the acquired immunodeficiency syndrome (AIDS) (n = 25), AIDS-related complex (n = 14), and HIV-seropositive men with only lymphadenopathy or no symptoms (n = 27). Controls were HIV-seronegative homosexual men (n = 22) and HIV-seronegative heterosexuals (n = 16). INTERVENTIONS: Subjects were immunized with inactivated vaccines containing 15 micrograms of each of the following influenza virus hemagglutinins: A/Taiwan/1/86 (HINI), A/Mississippi/1/85 (H3N2), A/Chile/1/83 (HINI), and B/Ann Arbor/1/86. MEASUREMENTS AND MAIN RESULTS: Fourfold or greater antibody responses occurred less frequently in subjects with HIV infections than in HIV-seronegative controls. Protective levels (1:64 or greater) of hemagglutination inhibition antibodies were attained by 94% to 100% of HIV-seronegative controls, 52% to 89% of HIV-seropositive asymptomatic subjects, and 13% to 50% of subjects with AIDS or AIDS-related complex. No increase in the prevalence or level of serum HIV p24 antigen or clinical deterioration was detected among HIV-infected persons after influenza immunization. CONCLUSIONS: Because of the poor antibody responses to influenza vaccines among HIV-infected subjects, even in many with no or minimal symptoms, alternative strategies for preventing influenza, such as booster doses of influenza vaccine, prophylaxis with amantidine, or both should be considered.

AIDS-Related Complex↗
PubMed1988

A prospective study of platelets and plasma proteolytic systems during the early stages of Rocky Mountain spotted fever.

We prospectively examined early changes in platelets and plasma proteolytic systems in 12 vaccinated and 6 unvaccinated volunteers in whom Rocky Mountain spotted fever developed after challenge with Rickettsia rickettsii. The platelet counts declined while the plasma concentration of beta-thromboglobulin and the ratio of beta-thromboglobulin to platelet factor 4 increased, indicating in vivo activation of platelets. Plasma levels of antithrombin III decreased and levels of fibrinopeptide A increased, indicating in vivo activation of the coagulation system. Plasma fibrinogen levels peaked at 24 hours and gradually declined; this is consistent with the behavior of fibrinogen as an acute-phase reactant. Prolongation of the prothrombin time and a decrease in plasma levels of factor VII in the absence of evidence of liver injury suggested possible activation of the extrinsic pathway of coagulation. A decline in plasma prekallikrein levels with an increase in plasma C1-inhibitor-kallikrein complexes suggested activation of kallikrein, probably through the intrinsic coagulation system. Elevations in levels of plasma fibrin-degradation products and alpha 2-antiplasmin-plasmin complexes with declines in plasminogen and alpha 2-antiplasmin levels provided evidence of activation of the fibrinolytic system. Elevated plasma levels of tissue plasminogen activator and von Willebrand factor reflected endothelial stimulation. Thus, even early in the course of Rocky Mountain spotted fever that is treated promptly, there is activation of platelets, coagulation pathways, and the fibrinolytic system. These changes may be related to endothelial perturbation, a major pathogenetic mechanism in the disorder.

Antithrombin III↗
PubMed1988

Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold-adapted vaccine recombinant in which vaccine-associated illness occurred in normal volunteers.

Live attenuated cold-adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold-adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten- and 100-fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold-adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.

Adult↗
PubMed1988

Experimental Campylobacter jejuni infection in humans.

Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain.

Adult↗
PubMed1988

Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults.

The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.

Adult↗
PubMed1988

Volunteer studies of deletion mutants of Vibrio cholerae O1 prepared by recombinant techniques.

Vibrio cholerae O1 A-B- vaccine strain JBK 70 and A-B+ CVD 101 prepared by recombinant DNA techniques from pathogenic EI Tor Inaba N16961 and classical Ogawa 395, respectively, were fed to 38 volunteers in single doses of 10(4) to 10(10). Although severe diarrhea did not occur in any vaccine, more than one-half developed mild diarrhea. These attenuated strains colonized well and elicited prominent vibriocidal and antitoxic (CVD 101) antibody responses. Recipients of a single dose of JBK 70 were significantly protected when challenged with 10(6) wild-type N16961. Diarrhea occurred in 7 of 8 controls but in only 1 of 10 vaccines (P less than 0.003, 89% vaccine efficacy), demonstrating the potency of immune mechanisms that do not involve cholera antitoxin. Further derivatives were prepared to explore the pathogenesis of the residual diarrhea, considering that either intestinal colonization by the vaccine itself or accessory toxins might be responsible. CVD 102, an auxotrophic mutant of CVD 101, did not cause diarrhea but colonized poorly and elicited feeble immune responses. Derivatives of JBK 70 and CVD 101 (CVD 104 and 105) deleted of genes encoding the EI Tor hemolysin still caused mild diarrhea. Genetically engineered strains can be colonizing, highly immunogenic, and protective single-dose oral vaccines, but they must be further attenuated before they can be considered for use as public health tools.

ABO Blood-Group System↗
PubMed1988

Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines.

Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.

Adult↗
PubMed1988

Susceptibility to virus infection with exposure to nitrogen dioxide.

The interaction between nitrogen dioxide (NO2) exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, blinded trial that was conducted in an environmentally controlled research chamber over a three-year period. Healthy, non-smoking volunteers, 18 to 35 years old, who were seronegative to influenza A/Korea/82 (H3N2) virus, were randomly assigned either to breathe filtered clean air (clean air group) or nitrogen dioxide (exposure group) for two hours a day for three consecutive days. The nitrogen dioxide concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects after the second day of exposure. Only one of the 152 volunteers had any symptoms, and that subject had only a low-grade fever. No adverse changes in pulmonary function or nonspecific airway reactivity to methacholine were observed after 2 or 3 ppm nitrogen dioxide exposure, virus infection, or both. Infection was defined by virus recovery, a four-fold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups exposed to nitrogen dioxide and those breathing clean air were: 12/21 (2 ppm nitrogen dioxide) versus 15/23 (clean air) in Year 1; 17/22 (3 ppm nitrogen dioxide) versus 15/21 (clean air) in Year 2; and 20/22 (2 ppm nitrogen dioxide) and 20/22 (1 ppm nitrogen dioxide) versus 15/21 (clean air) in Year 3. Although the differences were not statistically significant, the groups exposed to 1 or 2 ppm nitrogen dioxide in the last year became infected more often (91 percent) than those breathing clean air (71 percent). The frequencies of infection in two of the four groups exposed to nitrogen dioxide were higher than the 56 to 73 percent infection rate observed in previous studies in healthy human volunteers with the same dose of ca-influenza A (H3N2) virus. Our findings suggest, but do not prove, that nitrogen dioxide alone may play a role in increasing the susceptibility of adults to respiratory virus infections.

Adolescent↗
PubMed1987

Association between O blood group and occurrence and severity of diarrhoea due to Escherichia coli.

During studies of diarrhoea due to Escherichia coli in 316 adult volunteers, ABO and Rh blood group determinations were done to look for differences in the occurrence or severity of illness in association with certain blood groups. In studies using heat-labile enterotoxin-producing E. coli, volunteers with O blood group had a significantly higher attack rate for diarrhoea than persons with other blood groups. In contrast, in studies with enteropathogenic or heat-stable enterotoxin-producing E. coli, no association was found between occurrence of diarrhoea and ABO group. These studies, and previous studies finding a similarly increased susceptibility to cholera in persons with O blood group, suggest that the mechanism of increased risk involves an interaction between blood group substances and the similar enterotoxin produced by E. coli and Vibrio cholerae.

ABO Blood-Group System↗
PubMed1987

Prevention of shigellosis by a Salmonella typhi-Shigella sonnei bivalent vaccine.

We genetically modified attenuated Salmonella typhi strain Ty21a to express the form I O polysaccharide antigen of Shigella sonnei. Three doses of this bivalent, live oral vaccine strain (1-8 X 10(9) organisms/dose) were given to young adults who, along with unvaccinated controls, were challenged one month later with pathogenic S. sonnei. The vaccinees had 40% protection against diarrhea and 56% against Hematest-positive diarrhea. Two of three vaccine lots provided higher levels of protection (53% against diarrhea and 71% against Hematest-positive diarrhea), but the third lot, prepared for a large-scale field trial, demonstrated no protective efficacy. Vaccinees had serum and local intestinal immune responses to S. sonnei lipopolysaccharide, and the presence of specific serum IgA or IgG antibody before challenge with pathogenic S. sonnei was correlated with protection from illness. Some lots of this bivalent vaccine strain provide significant protection against S. sonnei disease, but the problem of lot-to-lot variability must be overcome.

Adult↗
PubMed1987

Protective efficacy of low-dose amantadine in adults challenged with wild-type influenza A virus.

The prophylactic efficacy of a low dose (100 mg) of amantadine hydrochloride against experimental challenge with influenza A/Texas/1/85 (H1N1) wild-type virus was determined in healthy adult volunteers in a placebo-controlled, double-blind, randomized trial. No side effects of the 100-mg dose were observed in the amantadine-treated volunteers. Compared with placebo, 100 mg of amantadine significantly reduced the frequency of illness (9 of 22 versus 2 of 22 volunteers, P less than 0.04) and provided 78% protection against influenza illness. The two ill volunteers in the amantadine group had rhinitis only, whereas most of the ill placebo controls developed both systemic and upper-respiratory-tract illness. Wild-type virus was recovered from 50% of the amantadine-treated volunteers, compared with 82% of the placebo controls. Of note, the infected amantadine recipients shed 100 times less virus and shed virus for half as many days as did the infected placebo recipients. Although amantadine restricted viral replication, it did not interfere with the development of an antibody response to influenza virus. These results indicate that in adults experimentally challenged with influenza wild-type virus, 100 mg of amantadine is effective both in the prevention of influenza illness and in the restriction of virus replication.

Administration, Intranasal↗
PubMed1987

Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin.

Natural protection from cholera is associated with local intestinal antibacterial and antitoxic antibodies, which appear to act synergistically. Although current parenteral cholera vaccines offer insufficient protection, new vaccines administered orally have more promise. Killed Vibrio cholerae, alone or given with the B subunit of cholera toxin, was evaluated in adult volunteers. Vaccinees, who received three doses of either vaccine, and unvaccinated controls ingested 10(6) V. cholerae organisms to determine the protective efficacy of the vaccines. The combination vaccine provided 64% protection, and the whole vibrio vaccine given alone provided 56% protection. In addition, illnesses in vaccines were milder than those in controls, and both vaccines gave complete protection against more severe disease. This substantial level of protection against a dose of V. cholerae that caused cholera in nearly 90% of controls suggests that these vaccines might provide at least as high a level of protection if given to the population of an endemic area. Indeed, a field efficacy trial is underway in Bangladesh, and preliminary data indicate a protective efficacy of 85% for a killed whole vibrio plus B subunit vaccine similar to that tested in volunteers and an efficacy of 58% for the killed whole vibrio vaccine alone. Thus, the studies in human volunteers were successful in predicting the substantial protection afforded by the vaccines in a cholera endemic area.

Administration, Oral↗