Mary Lou Clements

The Safety and Immunogenicity of a Human Immunodeficiency Virus Type 1 (HIV-1) Recombinant gp160 Candidate Vaccine in Humans

Objective: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp160) candidate vaccine in humans. Subjects: Healthy adult...

Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial

Typhoid fever remains an important public health problem in many areas of the world and an effective, non-reactogenic vaccine would be useful to control this disease. An attenuated Salmonella typhi strain (Ty21a), which has shown promise in previous trials, was evaluated in a controlled field trial in Santiago, Chile. In this trial, 82,543 schoolchildren were randomly assigned to receive one or two doses of Ty21a vaccine in enteric-coated capsules or placebo. The enteric-coated vaccine formulation was well tolerated and practical for mass oral immunization. In the first two years of surveillance, 213 cases of bacteriologically-confirmed typhoid fever were found in schoolchildren participating in the trial; annual rates in the placebo group were 139 and 227 per 100,000. Vaccine efficacy in the first two years after vaccination was 59% for two doses and 29% for one dose; no efficacy was found 3-5 years after vaccination. These results indicate that it will be necessary to identify a vaccine formulation and schedule for Ty21a S. typhi that is practical and provides high level protection for greater than 2 years.

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.

Induction of HIV-1-neutralising and syncytium-inhibiting antibodies in uninfected recipients of HIV-1IIIB rgp120 subunit vaccine.

A recombinant human immunodeficiency virus 1 IIIB (HIV-1IIIB) gp120 subunit vaccine (IIIB-rgp120/HIV-1, Genentech) was tested for safety and immunogenicity in a randomised, double-blind, placebo-controlled phase-I trial. HIV-1-seronegative adult volunteers received three 100 micrograms or 300 micrograms doses of IIIB-rgp120/HIV-1 in alum adjuvant (10 vaccinees in each group), or alum adjuvant alone (8 vaccinees), at 0, 4, and 32 weeks by intramuscular injection. The three injections were well tolerated in both vaccine groups. Antibodies that neutralised homologous HIV-1IIIB were induced in 9 of 10 recipients after three 300 micrograms doses, and 6 of these 9 sera also neutralised heterologous HIV-1SF2. A dose response was evident, since three 100 micrograms injections induced lower titres of HIV-1IIIB neutralising antibodies and in fewer recipients (5 of 9) than the higher dose, with no neutralisation of HIV-1SF2. Similarly, syncytia-inhibiting, CD4-rgp120-blocking, and HIV-1IIIB V3-binding antibodies were induced in a dose dependent manner. Response to the 300 micrograms per dose vaccination occurred in a larger proportion of volunteers and at higher mean titres than seen in previous human trials with other recombinant envelope subunit vaccines or live vaccinia-env priming followed by envelope subunit boosting.

Lactobacillus prophylaxis for diarrhea due to enterotoxigenic Escherichia coli.

In vitro and animal experiments indicated that lactobacilli might prevent Escherichia coli from colonizing the intestine and may produce substances counteracting enterotoxin. Lactinex, a commercial preparation of dried Lactobacillus acidophilus and L. bulgaricus, is marketed for uncomplicated diarrhea. Preliminary experiments in nonfasting volunteers indicated that lactobacilli in this preparation colonized the small intestine for up to 6 h. To evaluate the protective efficacy of Lactinex, a double-blind randomized study was carried out in which 48 volunteers (23 receiving Lactinex and 25 receiving placebos) were challenged with E. coli strains that produced heat-stable or heat-labile enterotoxins or both. No significant differences between the two groups were noted with respect to attack rate, incubation period, duration of diarrhea, volume and number of liquid stools, and coproculture yields. These data suggest that this lactobacillus preparations does not prevent or alter the course of enterotoxigenic E. coli diarrhea in adults. Lack of efficacy occurred despite efforts to maximize small bowel colonization, including administration of Lactinex in milk and in a 6-hour-interval regimen during 36 h before and 96 h after challenge.

Evaluation of a live attenuated bovine parainfluenza type 3 vaccine in two- to six-month-old infants.

BACKGROUND A safe and effective parainfluenza type 3 (PIV-3) virus vaccine is needed to prevent serious PIV-3-associated illness in infants younger than 6 months of age. In previous studies a live bovine PIV-3 (BPIV-3) vaccine, which was developed to prevent human PIV-3 (HPIV-3) disease, was shown to be safe, infectious, immunogenic and phenotypically stable in 6- to 36-month-old infants and children. METHODS The safety, infectivity and immunogenicity of a single dose of the BPIV-3 vaccine was evaluated in a randomized, placebo-controlled, double blinded trial in 19 infants 2 to 5.9 months of age and in 11 additional 6- to 36-month-old subjects. RESULTS The BPIV-3 vaccine was well-tolerated in both age groups and infected 92% of those younger than 6 months and 89% of those older than 6 months of age. Serum hemagglutination-inhibition (HAI) antibody responses to HPIV-3 and to BPIV-3, respectively, were detected in 42 and 67% of the younger infants, compared with 70 and 85% of the older subjects. In the younger infants we analyzed the rate of antibody response by titer of maternally acquired antibodies; low titer was defined as a preimmunization serum HAI titer < 1:8 and high titer was defined as a preimmunization serum HAI titer > or = 1:8. Young infants with a low titer of maternally acquired antibodies were significantly more likely to respond to the BPIV-3 vaccine that those with a high titer (89% vs. none for serum HAI response to BPIV-3; P = 0.02, Fishers exact test). CONCLUSIONS This study demonstrated that the BPIV-3 vaccine was safe and infectious in infants younger than 6 months of age and was also immunogenic in the majority of these young infants. Additional studies are needed to determine whether two or more doses will enhance the immunogenicity of the BPIV-3 vaccine in young infants and to assess its safety and immunogenicity when given simultaneously with routine childhood immunizations.

Medical Eligibility, Comprehension of the Consent Process, and Retention of Injection Drug Users Recruited for an Hiv Vaccine Trial

Injection drug users (IDUs) at high risk for human immunodeficiency virus (HIV) infection are being identified as a population for HIV vaccine trials. We studied willingness of drug users to enroll and their comprehension of consent procedures in the context of a Phase II trial at one site. Of 175 people screened for enrollment and whose data sets were complete, 119 (68%) were IDUs. Of the 71 who were eligible, 39 (55%) were IDUs. Exclusion of IDUs was usually for medical reasons. Using a 17-item true/false test, comprehension of the informed consent procedure was high (median score, 16 of 17 for IDUs and non-IDUs); only three subjects (all of whom were IDUs) were excluded from enrollment due to lack of comprehension. Follow-up rates were similar for IDUs and non-IDUs. These data suggest that recruitment of IDUs into HIV vaccine trials is feasible, that IDUs can comprehend and complete the informed consent procedures, and that they return for follow-up visits.

Safety and immunogenicity of a cold-adapted influenza A (H1N1) reassortant virus vaccine administered to infants less than six months of age.

A safe and effective influenza vaccine is needed to prevent serious influenza illness in infants younger than 6 months of age. The purpose of this study was to determine whether two doses of the cold‐adapted (ca) influenza A reassortant vaccine would be safe and immunogenic in this age group. In the first part of this study, infants received two doses of 105 or 108 50% tissue culture‐infectious dose (TCID50) of the ca influenza vaccine separately from routine immunizations. In the second part of this study two 106 TCID50 doses of the ca influenza vaccine were given with routine immunizations at 2 and 4 or 2 and 6 months of age. The ca influenza vaccine was well‐tolerated by participants in both parts of this study. Two doses of the ca influenza vaccine were immunogenic in infants who received them separately from routine immunizations; 83% of vaccinees developed protective titers of serum hemagglutination‐inhibition (HAI) antibody. In contrast, when the ca vaccine was administered with routine immunizations, protective HAI antibody titers were induced in only 20% of those immunized at 2 and 4 months of age and 50% of those immunized at 2 and 6 months of age. There were no statistically significant associations between HAI antibody response to ca influenza vaccination and dose schedule, presence of passively acquired maternal HAI antibody, ethnic group or breast‐feeding status. Young age at the time of first immunization, however, appeared to correlate with decreased response to the hemagglutinin antigen of the influenza A virus. Further studies are needed to determine whether a larger dose of vaccine (107 TCID50) could be used safely to improve the serum antibody response to influenza in very young infants.

Reduced infectivity of cold-adapted influenza A H1N1 viruses in the elderly : correlation with serum and local antibodies

To compare young and elderly adults in terms of their immune responses and rates of infection following intranasal vaccination with a live attenuated influenza virus.

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.