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1.
NPJ Vaccines ; 5: 77, 2020.
Article in English | MEDLINE | ID: mdl-32884842

ABSTRACT

Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone®, mammalian cell-derived Flucelvax® or recombinant HA (Flublok®). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.

2.
Epidemiol Infect ; 144(10): 2077-86, 2016 07.
Article in English | MEDLINE | ID: mdl-26931351

ABSTRACT

We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42-63] and 35% in Marshfield (95% CI 28-42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.


Subject(s)
Respiratory Tract Infections/epidemiology , Virus Diseases/epidemiology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Middle Aged , New York/epidemiology , Prospective Studies , Respiratory Tract Infections/virology , Seasons , Virus Diseases/virology , Wisconsin/epidemiology , Young Adult
3.
Rev Sci Tech ; 32(1): 239-47, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23837381

ABSTRACT

Bison (Bison bison) and elk (Cervus elaphus) in the greater Yellowstone ecosystem have long been infected with Brucella abortus. The continued culling of large numbers of Yellowstone bison to reduce the risk of brucellosis transmission to cattle could negatively affect long-term conservation. A desirable management objective is to reduce the level of B. abortus infection while conserving wildlife populations. Identifying the ecological factors that influence immune suppression and vulnerabilityto infection will help initiate effective control measures. Seasonal food restriction during pregnancy has the potential to limit resources available for immune defence and may be an important factor sustaining brucellosis in wild ungulate populations. Consequently, effective management practices will need to include a diverse range of integrated methods, which include maintaining separation of livestock and wildlife, managing habitat to reduce brucellosis transmission, and reducing disease prevalence in wildlife. The long-term success of these management practices will depend on sound science and support of the stakeholders involved.


Subject(s)
Animals, Wild , Bison , Brucellosis/veterinary , Conservation of Natural Resources/methods , Deer , Ecosystem , Animals , Brucellosis/epidemiology , Brucellosis/prevention & control , Food Deprivation , Seasons , United States/epidemiology
4.
Rev Sci Tech ; 32(1): 263-70, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23837383

ABSTRACT

Eradication of brucellosis from bison (Bison bison) and elk (Cervus elaphus) populations in the Greater Yellowstone Area is not possible with current technology. There are considerable uncertainties regarding the effectiveness of management techniques and unintended effects on wildlife behaviour and demography. However, adaptive management provides a framework for learning about the disease, improving suppression techniques, and lowering brucellosis transmission among wildlife and to cattle. Since it takes approximately three years after birth for female bison to become reproductively active and contribute to brucellosis transmission, there is an opportunity to implement actions such as vaccination and the selective removal of infectious bison based on age and assay results to reduce the potential for transmission. Older adult bison that have been exposed to the bacteria, but recovered from acute infection, could be retained in the population to provide some immunity (resistance) against future transmission. Through careful predictions, research, and monitoring, our understanding and technology will be improved and management actions can be adjusted to better achieve desired outcomes.


Subject(s)
Bison , Brucella abortus , Brucellosis/veterinary , Conservation of Natural Resources/methods , Deer , Animals , Animals, Wild , Brucella Vaccine/immunology , Brucellosis/epidemiology , Brucellosis/prevention & control , Population Surveillance , Seroepidemiologic Studies , United States/epidemiology
5.
Vaccine ; 28(2): 379-85, 2009 Dec 11.
Article in English | MEDLINE | ID: mdl-19879222

ABSTRACT

Alternative substrates for influenza vaccine production are needed to ensure adequate supplies. We evaluated the relative safety and immunogenicity of recombinant hemagglutinin (rHA) or trivalent inactivated vaccine (TIV) among 869 > or =65-year-old subjects in a randomized clinical trial. Virologic surveillance for influenza-like illness (ILI) was conducted during the 2006-2007 epidemic. Vaccines were well tolerated. Seroconversion rates vs. influenza A/H1N1 and H3N2 antigens were superior in the rHA group, but were inferior vs. influenza B; however, results for influenza B are confounded since the vaccine antigens were different. ILI frequencies were low and similar in both groups. Studies assessing relative immunogenicity of vaccines using identical B Ags are warranted.


Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza Vaccines/immunology , Recombinant Proteins/immunology , Aged , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Multicenter Studies as Topic , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/immunology
6.
Scand J Infect Dis ; 33(7): 542-4, 2001.
Article in English | MEDLINE | ID: mdl-11515767

ABSTRACT

Joining polysaccharide antigens to protein increases immunogenicity in infants. In older adults, using conjugation to protein carriers to improve the immune response to pneumococcal polysaccharide vaccine has thus far proved disappointing. Low immunity to the carrier protein in the elderly may explain the failure of conjugated vaccines to elicit a T-cell-dependent response. We immunized 49 older adults (ages 60-78) and 50 younger adults (ages 18-45) with either 23-valent pneumococcal polysaccharide (PS) vaccine or 5-valent CRM197-conjugated pneumococcal oligosaccharide. Sera obtained before and after vaccination were analyzed for antibody to pneumococcal serotypes 14 and 6B and diphtheria toxin by ELISA. Baseline diphtheria toxin antibody level was lower in older adults than in younger adults (0.31 and 0.88 IU/ml, respectively; p < 0.0001). Adults with higher diphtheria antibody level had a higher antibody level to PS type 6B after vaccination than those with lower diphtheria antibody level (9.9 vs. 3.5 microg/ml, respectively; p = 0.01). Antibody level to PS type 14 was higher, but differed by baseline anti-diphtheria antibody level only when the older group was evaluated alone. Low levels of antibody to diphtheria protein may explain some of the lower responses to conjugate pneumococcal vaccine in older adults.


Subject(s)
Antibodies, Bacterial/blood , Corynebacterium diphtheriae/immunology , Pneumococcal Infections/drug therapy , Pneumococcal Vaccines/therapeutic use , Adult , Aged , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Middle Aged , Treatment Outcome
7.
J Biol Chem ; 276(30): 28613-9, 2001 Jul 27.
Article in English | MEDLINE | ID: mdl-11358970

ABSTRACT

Vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that can be activated by capsaicin and other vanilloids as well as by protons and heat. In the present study, we have analyzed the oligomeric state of VR1. Co-immunoprecipitation of differently tagged VR1 molecules indicated that VR1 can form oligomers. Using two different heterologous VR1 expression systems as well as endogenous VR1 expressed in dorsal root ganglion cells, we analyzed oligomer formation using perfluoro-octanoic acid polyacrylamide gel electrophoresis. Results were confirmed both with chemical cross-linking agents as well as through endogenous cross-linking mediated by transglutaminase. Our results clearly show that VR1 forms multimers in each of the expression systems with a homotetramer as a predominant form. The oligomeric structure of VR1 may contribute to the complexity of VR1 pharmacology. Finally, differences in glycosylation between the systems were observed, indicating the need for caution in the use of the heterologous expression systems for analysis of VR1 properties.


Subject(s)
Receptors, Drug/chemistry , Animals , Blotting, Western , CHO Cells , COS Cells , Caprylates/chemistry , Cricetinae , Cross-Linking Reagents/pharmacology , Dimerization , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Fluorocarbons/chemistry , Green Fluorescent Proteins , Ligands , Luminescent Proteins/metabolism , Plasmids/metabolism , Precipitin Tests , Protein Structure, Quaternary , Protons , Recombinant Fusion Proteins/metabolism , TRPV Cation Channels , Transfection , Transglutaminases/metabolism
8.
Vaccine ; 19(13-14): 1732-7, 2001 Feb 08.
Article in English | MEDLINE | ID: mdl-11166898

ABSTRACT

Recent outbreaks of avian influenza in humans have demonstrated the need for vaccines for influenza viruses with pandemic potential. Recombinant hemagglutinins are an attractive option for such vaccines because they do not require handling potentially highly pathogenic influenza viruses for vaccine production. In order to evaluate the immunogenicity, optimum dosing and timing of administration of a recombinant baculovirus-expressed H5 HA (rH5) in humans, 147 healthy adults were assigned randomly to receive intramuscular rH5 as two doses of 25, 45 or 90 microg each, one dose of 90 microg followed by a dose of 10 microg, or two doses of placebo, at intervals between doses of 21, 28 or 42 days. All doses of rH5 were well tolerated. The rH5 vaccine was modestly immunogenic at high dose. Neutralizing antibody responses to a titer of 1:80 or greater were seen in 23% (14/60) of individuals after a single dose of 90 microg, and in 52% (15/29) after two doses of 90 microg. Varying intervals between doses from 21 to 42 days had no significant effect on antibody responses to vaccination. These results suggest that baculovirus-expressed H5 HA can induce functional antibody in individuals who have not had prior exposure to H5 viruses, but that further studies to improve the immunogenicity of the vaccine are needed.


Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A virus/immunology , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/immunology , Adult , Antibodies, Viral/immunology , Dose-Response Relationship, Immunologic , Enzyme-Linked Immunosorbent Assay , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Immunization Schedule , Kinetics , Neutralization Tests , Vaccination
9.
Am J Manag Care ; 6(5 Suppl): S265-75, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10977473

ABSTRACT

Influenza epidemics account for more than 20,000 deaths in the United States each year, as well as substantial morbidity, medical costs, and time away from work and school. Since the 1950s, the principal weapon against these seasonal epidemics has been killed virus vaccine formulations. Despite massive efforts to immunize at-risk individuals against influenza, not everyone receives the vaccine. In addition, use of some drugs, such as amantadine and rimantadine, can lead to the development of drug resistant viruses in infected individuals and to transmission of these viruses to susceptible individuals. The many factors that contribute to the high annual incidence of influenza virus infections mandate prompt clinical recognition and appropriate patient management. Rapid diagnostic tests have been developed that may make it possible to avoid the use of antibacterial drugs, quickly decide whether isolation of infected patients is needed, and discharge hospitalized patients sooner.


Subject(s)
Influenza, Human/diagnosis , Fever/virology , Fluorescent Antibody Technique , Humans , Influenza, Human/virology , Orthomyxoviridae/isolation & purification , Serologic Tests
11.
JAMA ; 283(8): 1016-24, 2000 Feb 23.
Article in English | MEDLINE | ID: mdl-10697061

ABSTRACT

CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.


Subject(s)
Acetamides/therapeutic use , Antiviral Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Influenza, Human/drug therapy , Neuraminidase/antagonists & inhibitors , Acetamides/administration & dosage , Acute Disease , Adult , Antiviral Agents/administration & dosage , Double-Blind Method , Drug Administration Schedule , Enzyme Inhibitors/administration & dosage , Female , Humans , Influenza, Human/complications , Influenza, Human/physiopathology , Male , Middle Aged , Oseltamivir , Severity of Illness Index , Statistics, Nonparametric
12.
Vaccine ; 18(16): 1690-5, 2000 Feb 25.
Article in English | MEDLINE | ID: mdl-10689150

ABSTRACT

Inactivated influenza vaccine (Ivac) has had an important impact on reducing attack rates of influenza and reducing the severity of illness amongst the vaccinees who still acquire infection. Ivac is most efficacious amongst young, otherwise healthy subjects and least effective against elderly at high risk. This is in part because Ivac does not appear to significantly reduce infection rates and in part because response rate and final antibody titer are lower in the elderly. Therefore Ivac does not eliminate disease in the elderly who are prone to complications when any virus replication occurs. Simultaneous administration of intra-nasal live attenuated influenza vaccine (Livac) and Ivac reduces the infection rate and thus illness rate amongst high-risk elderly. Presumably this is because of the ability of Livac to stimulate secretory antibody which neutralizes virus at the mucosal surface. Other approaches are examining the benefit of baculovirus recombinant vaccine or adjuvanted Ivac to determine if the higher serum antibody these vaccines produce compared to Ivac, will diffuse onto the mucosal surfaces and in a similar fashion, neutralize virus at that site.


Subject(s)
Influenza Vaccines/pharmacology , Influenza, Human/immunology , Influenza, Human/prevention & control , Adolescent , Adult , Aged , Aging/immunology , Antibodies, Viral/blood , Baculoviridae/genetics , Double-Blind Method , Humans , Immunity, Mucosal , Influenza Vaccines/administration & dosage , Middle Aged , Orthomyxoviridae/immunology , Safety , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/pharmacology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/pharmacology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/pharmacology
13.
Vaccine ; 18(9-10): 899-906, 1999 Dec 10.
Article in English | MEDLINE | ID: mdl-10580204

ABSTRACT

Trivalent, live, cold-adapted influenza vaccine (CAIV-T) is highly effective in the prevention of influenza in children, and a variety of monovalent and bivalent cold-adapted influenza vaccines have been efficacious in adults. In order to determine the efficacy of CAIV-T in healthy adults, we administered CAIV-T, trivalent inactivated influenza vaccine (TIV) or placebo to 103 adults in randomized double-blind fashion, and then challenged those subjects who had pre-screening serum hemagglutination-inhibition antibody titers of 1:8 or less with wild-type influenza viruses corresponding to the strains contained in the vaccine. CAIV-T was well tolerated. Upon challenge with wild-type influenza virus, laboratory documented influenza illness (respiratory symptoms with either isolation of wild-type influenza virus from nasal secretions or 4-fold and/or greater HAI antibody response to challenge) occurred in 14/31 (45%) placebo recipients, 4/32 (13%) TIV recipients, and 2/29 (7%) CAIV-T recipients. The estimated protective efficacy of CAIV-T was therefore 85% and of TIV was 71%. These results are consistent with those of previous studies using monovalent preparations of cold-adapted influenza vaccine in this model, and indicate that CAIV-T will be an effective means to prevent influenza illness in adults.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H3N2 Subtype , Influenza A virus/immunology , Influenza B virus/immunology , Influenza Vaccines , Vaccines, Synthetic , Administration, Intranasal , Adult , Cold Temperature , Humans , Influenza, Human/prevention & control , Injections, Intramuscular , Vaccines, Combined/immunology
14.
J Infect Dis ; 180(6): 2023-6, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10558962

ABSTRACT

Granulocyte macrophage colony-stimulating factor (GM-CSF) has shown promise as an adjuvant to improve the kinetics and magnitude of the immune response after vaccination. It was hypothesized that GM-CSF given intramuscularly (IM) with hepatitis B vaccine would result in increased seroconversion rates and antibody titers. In total, 108 healthy volunteers (18-45 years old) received recombinant hepatitis B vaccine IM at 0, 1, and 6 months and were randomized to receive either concurrent GM-CSF (80 or 250 microgram) or placebo IM with the first two vaccinations. The percentages of subjects achieving a protective level of antibody at day 56 were 58.3%, 58.8%, and 58.3% in the placebo and 80- and 250-microgram GM-CSF arms, respectively. The geometric mean titers of antibody measured on days 28, 56, and 189 were not statistically different between arms. GM-CSF given immediately before recombinant hepatitis B vaccination was safe and well tolerated but did not appear to provide significant adjuvant activity at this dose.


Subject(s)
Adjuvants, Immunologic , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Hepatitis B Vaccines/immunology , Vaccination , Adolescent , Adult , Double-Blind Method , Female , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/adverse effects , Humans , Male , Recombinant Proteins
15.
JAMA ; 282(13): 1240-6, 1999 Oct 06.
Article in English | MEDLINE | ID: mdl-10517426

ABSTRACT

CONTEXT: Influenza virus neuraminidase is thought to be essential for virus replication in humans; however, to date, available neuraminidase inhibitors are limited to zanamivir, which is topically administered. OBJECTIVE: To determine the safety, tolerability, and antiviral activity of oral neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and the early treatment of influenza in experimentally infected humans. DESIGN: Two randomized, double-blind, placebo-controlled trials conducted between June and July 1997. SETTING: Individual hotel rooms; 2 large US university medical schools. PARTICIPANTS: A total of 117 healthy adult volunteers (aged 18-40 years; median age, 21 years) who were susceptible (hemagglutination-inhibition antibody titer < or =1:8). INTERVENTIONS: All subjects were inoculated intranasally with influenza A/Texas/36/91 (H1N1) virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n = 12], 100 mg twice daily [n = 12], or matching placebo [n = 13], starting 26 hours before virus inoculation) was administered. For the treatment study, the same drug was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching placebo [n = 16], in each group starting 28 hours after inoculation). All regimens were continued for 5 days. MAIN OUTCOME MEASURES: Comparing placebo groups with pooled treatment groups, for prophylaxis, outcomes included frequency of infection and viral shedding; for treatment, viral shedding in titers. RESULTS: In the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir recipients became infected (P = .16; efficacy, 61%); 6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P<.001; efficacy, 100%), and 33% of placebo but no oseltamivir recipient had infection-related respiratory illness (P<.01). Among infected subjects in the treatment study (n = 69), the viral titer area under the curve of the combined oseltamivir groups (n = 56) was lower (median [interquartile range [IQR]], 80 [23-151] vs 273 [79-306] log10 tissue culture-infective doses50 per milliliter x hour; P = .02) than the placebo group (n = 13), and the median (IQR) duration of viral shedding with therapy was reduced from 107 (83-131) to 58 (35-59) hours (P = .003). Oseltamivir treatment also reduced symptom scores (median [IQR] score-hours, 225 [97-349] vs 400 [189-645]; P = .05), and nasal proinflammatory cytokine levels. Transient mild to moderate nausea after dosing was observed in 15 (17%) of 88 oseltamivir and 2 (7%) of 29 placebo recipients (95% confidence interval for difference, -11% to 68%), which was largely prevented by ingestion with food. CONCLUSIONS: In these trials, prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza.


Subject(s)
Amines/therapeutic use , Enzyme Inhibitors/therapeutic use , Influenza A virus/isolation & purification , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Neuraminidase/antagonists & inhibitors , Administration, Oral , Adolescent , Adult , Amines/administration & dosage , Amines/adverse effects , Area Under Curve , Dose-Response Relationship, Drug , Double-Blind Method , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Female , Humans , Male , Nausea/chemically induced , Nose/virology , Oseltamivir
16.
Ann Intern Med ; 131(6): 430-3, 1999 Sep 21.
Article in English | MEDLINE | ID: mdl-10498559

ABSTRACT

BACKGROUND: Although influenza vaccination is recommended in persons infected with HIV-1, its efficacy is unknown. OBJECTIVE: To assess the immunogenicity, efficacy, and risks associated with influenza vaccination in persons infected with HIV-1. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient military clinic. PATIENTS: 102 patients with HIV-1 infection. INTERVENTION: Influenza vaccine (n = 55) or saline placebo (n = 47). MEASUREMENTS: Influenza antibody titers, CD4+ cell counts, and plasma HIV-1 RNA levels at baseline, 1 month after immunization, and 3 months after immunization; viral cultures from persons presenting with respiratory illness; and respiratory symptom interview. RESULTS: Twenty-three placebo recipients (49%) and 16 vaccine recipients (29%) reported respiratory symptoms (P = 0.04). Ten placebo recipients but no vaccine recipients had laboratory-confirmed symptomatic influenza (P < 0.001) (protective efficacy, 100% [95% CI, 73% to 100%]). No effect on plasma HIV-1 RNA levels or CD4+ cell counts was noted. CONCLUSION: Influenza vaccination is highly effective in HIV-1-infected persons and does not seem to be associated with substantial changes in viral load or CD4 cell count.


Subject(s)
HIV Infections/immunology , Immunocompromised Host , Influenza A virus , Influenza Vaccines , Influenza, Human/prevention & control , Vaccination , CD4 Lymphocyte Count , Double-Blind Method , HIV Infections/virology , HIV-1/genetics , Humans , RNA, Viral/blood , Viral Load
17.
J Interferon Cytokine Res ; 19(7): 751-5, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10454345

ABSTRACT

Tumor necrosis factor-alpha (TNF-alpha) is often measured in the serum or plasma of patients with severe infections, and marked elevation correlates with poor outcome. The relationship of TNF-alpha to protection from disease is frequently not observed because prospective studies of infectious agents are difficult to perform. We took advantage of a human antiviral influenza challenge study to correlate TNF-alpha production with seroconversion and symptom development. TNF-alpha production was measured by ELISA in the plasma compartment or was measured by intracellular production at the single cell level in the monocyte gated population. Monocyte TNF-alpha was associated with asymptomatic seroconversion, whereas there was no change in the plasma at the times measured. Measurement of TNF-alpha at the single cell level by flow cytometry may allow for better differentiation of the protective role of this cytokine in future studies.


Subject(s)
Influenza A virus/physiology , Influenza, Human/blood , Leukocytes, Mononuclear/virology , Tumor Necrosis Factor-alpha/biosynthesis , Adolescent , Adult , Flow Cytometry , Humans , Leukocytes, Mononuclear/metabolism
18.
J Infect Dis ; 179(5): 1124-31, 1999 May.
Article in English | MEDLINE | ID: mdl-10191213

ABSTRACT

Determination of antigen-specific cytokine responses of T lymphocytes after vaccination is made difficult by the low frequency of responder cells. In order to detect these responses, the profile of intracellular cytokines was analyzed using flow cytometry after antigenic expansion. Peripheral blood mononuclear cells were stimulated with antigens for 5 days, further expanded with interleukin (IL)-2, and then restimulated on day 10. Cytokine production was detected by intracellular staining with monoclonal antibodies after saponin-based permeabilization. Influenza expansion resulted in specific interferon-gamma (IFN-gamma) production of 6%-20%, with less IL-4 production (0%-2%). Tetanus toxoid resulted in even greater production. IL-4 and IFN-gamma were produced mainly by memory cells of the CD45RO+ phenotype. IFN-gamma production was contributed by both CD4 and CD8 populations. These methods were then applied to a clinical trial of a candidate human immunodeficiency virus type 1 vaccine. Antigen-specific increases in IFN-gamma were measured, which corresponded to antibody production, lymphoproliferation, and skin testing.


Subject(s)
AIDS Vaccines/immunology , Antigens, Viral/immunology , Cytokines/biosynthesis , Influenza Vaccines/immunology , T-Lymphocytes/immunology , Adult , Antibodies, Monoclonal , Cells, Cultured , Double-Blind Method , Flow Cytometry , HIV Envelope Protein gp120/immunology , Humans , Immunologic Memory , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Interferon-gamma/biosynthesis , Leukocytes, Mononuclear , Lymphocyte Activation , Mitogens/immunology , Staining and Labeling , Tetanus Toxoid/immunology , Vaccination , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology
19.
Vaccine ; 16(18): 1756-60, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9778752

ABSTRACT

We have evaluated the use of live cold-adapted influenza A and B virus vaccines in the elderly. Cold-adapted influenza A and B virus vaccines are safe and modestly immunogenic in individuals over 65 years of age. However, our studies and those of other groups have shown that immune response to cold-adapted vaccines in this age group are modest. Administration of combined cold-adapted influenza A and inactivated influenza vaccine has resulted in slightly higher frequencies of local and systemic humoral immune responses than inactivated vaccine alone in some, but not all, studies. In a double-blind field trial conducted in nursing homes over a 3 year period, combined cold-adapted influenza A (H3N2) and trivalent inactivated influenza vaccine resulted in a 60% decrease (95% CI, 18-82%) in the rate of laboratory documented influenza A compared with inactivated vaccine alone. Further studies of multivalent cold-adapted influenza vaccines used in combination with inactivated vaccine should be performed.


Subject(s)
Influenza A virus/immunology , Influenza B virus/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Aged , Antibodies, Viral/biosynthesis , Cold Temperature , Double-Blind Method , Enzyme-Linked Immunosorbent Assay , Female , Hemagglutination Tests , Humans , Influenza, Human/immunology , Male , Middle Aged , Nursing Homes , Vaccines, Attenuated/immunology
20.
Vaccine ; 16(9-10): 1039-42, 1998.
Article in English | MEDLINE | ID: mdl-9682356

ABSTRACT

Annual influenza vaccine is recommended for persons with HIV infection. Recent reports indicate that immunizations may increase HIV replication in infected individuals. Forty-seven HIV-infected patients were randomized to influenza vaccine or saline placebo using a double blind study design. One month after vaccination, plasma HIV-1 RNA increased in the vaccinated but not placebo group (p = 0.029). At 3 months, CD4% dropped an average of 1.6 points in the vaccinated group compared to an increase of 0.1 points in the placebo group (p = 0.039). Patients on stable antiretroviral regimens had CD4% drop an average of 2.3 points in the vaccinated group at 3 months versus 0.1 points in the placebo group (p = 0.015). It is concluded that HIV-infected patients are at risk for increased HIV replication and decreases in CD4% following influenza vaccination. Since influenza has not been associated with significant morbidity in this population, further study of routine influenza vaccination for HIV-infected patients is warranted.


Subject(s)
HIV Infections/immunology , HIV Infections/therapy , Influenza Vaccines/pharmacology , AIDS-Related Opportunistic Infections/immunology , AIDS-Related Opportunistic Infections/prevention & control , Adult , Antibodies, Viral/blood , CD4 Lymphocyte Count , Double-Blind Method , Female , HIV Infections/virology , HIV-1/isolation & purification , HIV-1/physiology , Humans , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Influenza, Human/complications , Influenza, Human/immunology , Influenza, Human/prevention & control , Male , Orthomyxoviridae/immunology , RNA, Viral/blood , Viremia/immunology , Viremia/therapy , Viremia/virology , Virus Replication
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