Geoffrey J Gorse

Publications of Geoffrey J Gorse

• DNA and Modified Vaccinia Ankara (MVA) Human Immunodeficiency Virus Type 1 (HIV-1) Vaccines Encoding Multiple Cytotoxic and Helper T-Lymphocyte Epitopes Are Safe But Weakly Immunogenic in HIV-1-Uninfected, Vaccinia-Naive Adults.

  Authors: Geoffrey J Gorse, Mark J Newman, Allan Decamp, Christine Mhorag Hay, Stephen C De Rosa, Elizabeth Noonan, Brian D Livingston, Jonathan D Fuchs, Spyros A Kalams, Farah L Cassis-Ghavami

  Clinical and vaccine immunology : CVI. 03/2012;

  We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia Ankara virus vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiencyWe evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia Ankara virus vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or interferon-γ production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses including production of tumor necrosis factor-α and perforin were detected. Vaccinia-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe, but ineffective at inducing HIV-1-specific immune responses, and induced far weaker responses than MVA vaccines expressing the entire open reading frame of HIV-1 proteins.

• Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum.

  Authors: Geoffrey J Gorse, Gira B Patel, Joseph N Vitale, Theresa Z O'Connor

  Clinical and vaccine immunology : CVI. 10/2010; 17(12):1875-80.

  Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1). ByLittle is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1). By enzyme-linked immunosorbent assay, we measured anti-HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U.S. sites from 105 adults aged 50 years and older (mean age, 67 ± 9 years) with chronic obstructive pulmonary disease. Most patients (95 [90%]) had at least one more chronic disease. More patients had serum antibody to each HCoV strain (104 [99%] had antibody to HCoV-229E, 105 [100%] had antibody to HCoV-OC43, 103 [98%] had antibody to HCoV-NL63, and 96 [91%] had antibody to HCoV-HKU1) than had antibody to each HCoV strain in nasal wash specimens (12 [11%] had antibody to HCoV-229E, 22 [22%] had antibody to HCoV-OC43, 8 [8%] had antibody to HCoV-NL63, and 31 [31%] had antibody to HCoV-HKU1), respectively (P < 0.0001). The proportions of subjects with IgA antibodies in nasal wash specimens and the geometric mean IgA antibody titers were statistically higher for HCoV-OC43 and -HKU1 than for HCoV-229E and -NL63. A higher proportion of patients with heart disease than not had IgA antibodies to HCoV-NL63 (6 [16%] versus 2 [3%]; P = 0.014). Correlations were highest for serum antibody titers between group I strains (HCoV-229E and -NL63 [r = 0.443; P < 0.0001]) and between group II strains (HCoV-OC43 and -HKU1 [r = 0.603; P < 0.0001]) and not statistically significant between HCoV-NL63 and -OC43 and between HCoV-NL63 and -HKU1. Patients likely had experienced infections with more than one HCoV strain, and IgG antibodies to these HCoV strains in serum were more likely to be detected than IgA antibodies to these HCoV strains in nasal wash specimens.

• Randomized, Double-Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High-Dose and Standard-Dose Influenza Vaccine in Adults 65 Years of Age and Older.

  Authors: Ann R Falsey, John J Treanor, Nadia Tornieporth, Jose Capellan, Geoffrey J Gorse

  The Journal of infectious diseases. 08/2009; 200(2):172-180.

  Background. Influenza-associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high-doseBackground. Influenza-associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high-dose (HD) trivalent, inactivated influenza vaccine was developed. Methods. A multicenter, randomized, double-blind controlled study was conducted to compare HD vaccine (which contains 60 mug of hemagglutinin per strain) with the licensed standard-dose (SD) vaccine (which contains 15 mug of hemagglutinin per strain) in adults 65 years of age. Results. HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects. There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine, compared with those who received SD vaccine. Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1, 609 for H3N2, and 69 for B strain; for those who received SD vaccine, mean postvaccination titers were as 67 for H1N1, 333 for H3N2, and 52 for B strain. The HD vaccine met superiority criteria for both A strains, and the responses for B strain met noninferiority criteria. Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine, for all strains. Local reactions were more frequent in individuals who received HD vaccine, but the reactions were mild to moderate. Conclusions. There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine, compared with that induced by SD vaccine, without an attendant increase in the rate or severity of clinically relevant adverse reactions. These results suggest that the high-dose vaccine may provide improved protective benefits for older adults. Trial registration. ClinicalTrials.gov identifier: NCT00391053 .

• Human Coronavirus and Acute Respiratory Illness in Older Adults with Chronic Obstructive Pulmonary Disease.

  Authors: Geoffrey J Gorse, Theresa Z O'Connor, Susan L Hall, Joseph N Vitale, Kristin L Nichol

  The Journal of infectious diseases. 04/2009; 199(6):847-857.

  Background. The clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition. Methods. HCoV infection was determined on the basis of aBackground. The clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition. Methods. HCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction. Laboratory-documented influenza (LDI) was detected by serologic assay and culture. HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998-99 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were 50 years old and who received influenza vaccines. Results. HCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses. In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13-0.58]). A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness. Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization. A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1. Conclusions. The frequencies of HCoV and LDI illnesses were similar. HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization.

• Comparison of the Safety and Immunogenicity of 2 Respiratory Syncytial Virus (RSV) Vaccines- Nonadjuvanted Vaccine or Vaccine Adjuvanted with Alum-Given Concomitantly with Influenza Vaccine to High-Risk Elderly Individuals.

  Authors: Ann R Falsey, Edward E Walsh, Jose Capellan, Stefan Gravenstein, Maria Zambon, Eddy Yau, Geoffrey J Gorse, Robert Edelman, Frederick G Hayden, Janet E McElhaney, Kathleen M Neuzil, Kristen L Nichol, Eric A F Simões, Peter F Wright, Valérie M-P Sales

  The Journal of infectious diseases. 11/2008; 198(9):1317-1326.

  Background. @nbsp; Respiratory syncytial virus (RSV) has been recognized recently as an important adult pathogen. Methods. @nbsp; This randomized, double-blind, placebo-controlled study was designedBackground. @nbsp; Respiratory syncytial virus (RSV) has been recognized recently as an important adult pathogen. Methods. @nbsp; This randomized, double-blind, placebo-controlled study was designed to compare humoral responses to licensed trivalent influenza vaccine given concomitantly with 1 of 2 RSV vaccine formulations in persons >/=65 years old with cardiopulmonary disease. Hemagglutinin-inhibition assays and neutralization assays were used to measure levels of antibody to influenza and RSV, respectively. Subjects with respiratory illnesses during subsequent winters were tested for RSV and influenza by reverse-transcriptase polymerase chain reaction and serologic analysis. Results. @nbsp; Neither RSV vaccine formulation had an effect on the humoral response to influenza vaccination, and both RSV vaccines were well tolerated by 1169 participants. The immunogenicity of the nonadjuvanted vaccine was judged superior on the basis of mean postvaccination neutralizing antibody titers (12.5 vs. 12.1) and the percentage of subjects for whom >/=4-fold increases in neutralizing titer were observed when acute-phase and convalescent-phase serum samples were compared (168 [44%] of 383 vs. 129 [33%] of 400). In year 1, the percentage of illnesses due to RSV was 7% (36 of 492 illnesses) and that due to influenza was 8% (40 of 492), compared with 6% (11 of 189) due to RSV and 11% (20 of 189) due to influenza in year 2. The incidence of RSV infection was not significantly different in the RSV vaccine and placebo groups. Conclusions. @nbsp; Although the safety and immunogenicity data of these RSV vaccines are encouraging, low rates of infection make it challenging to design efficacy trials.

• Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults.

  Authors: Geoffrey J Gorse, Lindsey R Baden, Margaret Wecker, Mark J Newman, Guido Ferrari, Kent J Weinhold, Brian D Livingston, Tonya L Villafana, Hongli Li, Elizabeth Noonan, Nina D Russell

  Vaccine. 02/2008; 26(2):215-23.

  We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), inWe evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized, double-blinded, placebo-controlled Phase 1 trial. Vaccine, at 0.5, 2.0, or 4.0mg doses, or placebo was injected four times over 6 months. Forty-two healthy, HIV-1-uninfected adults were enrolled. Using an interferon-gamma ELISPOT assay, a response to PADRE was detected in one vaccine recipient. Three vaccine recipients raised anti-HIV-1 CD8+ CTL measured by chromium-release assay. The vaccine was safe and well-tolerated, but only weakly immunogenic.

• Response to letter to the editor "Zink TK. Vaccine 2007;25(15):2766-7".

  Authors: Geoffrey J Gorse, Wendy Keitel, Harry Keyserling, David N Taylor, Michael Lock, Katia Alves, Julie Kenner, Lynne Deans, Marc Gurwith

  Vaccine. 11/2007; 25(42):7285-7.

• Impact of a winter respiratory virus season on patients with COPD and association with influenza vaccination.

  Authors: Geoffrey J Gorse, Theresa Z O'Connor, Stephen L Young, Michael P Habib, Janet Wittes, Kathleen M Neuzil, Kristin L Nichol

  Chest. 11/2006; 130(4):1109-16.

  BACKGROUND: We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzedBACKGROUND: We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzed for changes in spirometric and functional status, comparing patients with laboratory-documented influenza (LDI)-caused illness, non-LDI-caused respiratory illness, or no illness, and for association with influenza vaccination. METHODS: Patients received either IM trivalent inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal placebo (TP). We performed spirometry, measured the chronic lung disease severity index (CLDSI) score to assess functional status and well-being, and tested for influenza virus infection. RESULTS: Worsening in FEV(1), percentage of predicted FEV(1), and CLDSI score (p < 0.001) was associated with acute respiratory illness in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more likely to be associated with worsening in FEV(1) and CLDSI score acutely than non-LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL, 1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute respiratory illness) to be associated with better CLDSI score at the end of the study. Hospitalization was more frequent in patients with acute respiratory illness (p < 0.0001). CONCLUSIONS: Acute respiratory illness was associated with increased health-care utilization and obstruction to airflow, and worse functional status and well-being. At the end of the study, receipt of TC was associated with improvement and acute respiratory illness was associated with worsening in functional status and well-being.

• Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: a randomized, double-blinded, controlled, multicenter trial.

  Authors: Geoffrey J Gorse, Wendy Keitel, Harry Keyserling, David N Taylor, Michael Lock, Katia Alves, Julie Kenner, Lynne Deans, Marc Gurwith

  Vaccine. 09/2006; 24(33-34):5950-9.

  BACKGROUND: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. METHODS: Hundred healthy volunteersBACKGROUND: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. METHODS: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 microg of rPA102 in 82.5 microg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. FINDINGS: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p < 0.001) and the second (84.2% versus 35.4%; p < 0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 microg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. INTERPRETATION: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 microg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.

• Cellular immune responses in asymptomatic human immunodeficiency virus type 1 (HIV-1) infection and effects of vaccination with recombinant envelope glycoprotein of HIV-1.

  Authors: Geoffrey J Gorse, Ramona E Simionescu, Gira B Patel

  Clinical and vaccine immunology : CVI. 02/2006; 13(1):26-32.

  Effects of human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein vaccines on cell-mediated immune (CMI) responses were assessed in HIV-1-infected patients. Asymptomatic,Effects of human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein vaccines on cell-mediated immune (CMI) responses were assessed in HIV-1-infected patients. Asymptomatic, antiretroviral-treatment-naïve, HIV-1-infected patients with CD4(+) T-cell counts greater than 400/microl received multiple intramuscular injections of HIV-1 IIIB recombinant envelope glycoprotein (rgp160) vaccine or HIV-1 MN recombinant envelope glycoprotein (rgp120) vaccine (eight patients, referred to as the HIV-1 vaccinees) or placebo or hepatitis B vaccine (three patients, referred to as the controls). Lymphocyte proliferation in response to HIV-1 envelope glycoproteins, both homologous and heterologous to the HIV-1 immunogens, was absent prior to study treatment in all patients but increased significantly during the vaccination series and after the final vaccination in HIV-1 vaccinees (P < 0.05) and remained absent in control patients. In flow cytometric analyses of intracellular cytokines, T-cell receptor stimulation with an anti-CD3 antibody induced gamma interferon (IFN-gamma) expression by activated CD4(+) and CD8(+) lymphocytes at greater frequencies than did stimulation with recombinant envelope glycoprotein and p24 of HIV-1 (P < 0.05). Mean frequencies of HIV-1 envelope glycoprotein-stimulated, activated intra-cellular IFN-gamma-producing CD4(+) and CD8(+) lymphocytes and of interleukin-2-producing CD4(+) lymphocytes did not increase after vaccination, but cytokine-producing cells were detectable in some patients. Comparing pre- to post-HIV-1 vaccination time points, changes in frequencies of activated, IFN-gamma-producing CD4(+) cells correlated inversely with changes in lymphocyte proliferation in response to recombinant envelope glycoprotein in HIV-1 vaccinees (P < 0.05). Increased CMI responses to HIV-1 envelope glycoprotein measured by lymphocyte proliferation were associated with HIV-1 recombinant envelope glycoprotein vaccines.

• Immunity to influenza in older adults with chronic obstructive pulmonary disease.

  Authors: Geoffrey J Gorse, Theresa Z O'Connor, Frances K Newman, Mahendra D Mandava, Paul M Mendelman, Janet Wittes, Peter N Peduzzi

  The Journal of infectious diseases. 08/2004; 190(1):11-9.

  BACKGROUND: Chronically ill older adults constitute a population vulnerable for complications associated with influenza. Study of their immunity to influenza virus may help design better strategiesBACKGROUND: Chronically ill older adults constitute a population vulnerable for complications associated with influenza. Study of their immunity to influenza virus may help design better strategies to stimulate protective immune responses. METHODS: Immunogenicity of influenza vaccines and immune protection from natural influenza were assessed in older adults with chronic obstructive pulmonary disease as part of a vaccine efficacy trial. Subjects received either trivalent inactivated influenza virus vaccine (TVV) intramuscularly and trivalent live cold-adapted influenza virus vaccine (CAIV-T; n=1107) intranasally (inl) or TVV and placebo inl (P; n=1108). RESULTS: In the subsets of study subjects assessed, serum hemagglutination inhibition (HAI) and nasal-wash antihemagglutinin (HA) immunoglobulin (Ig) A and IgG antibody levels and anti-influenza virus CD8(+) cytotoxic T lymphocyte activity increased after immunization. Mean postimmunization nasal-wash IgA antibody levels to influenza A H3/HA and B HA were statistically higher in the TVV+CAIV-T group (n=957) than in the TVV+P group (n=951). Postimmunization serum HAI and nasal-wash IgA antibodies to influenza A/H3N2 and B viruses were associated with a reduced relative risk for natural influenza infection. CONCLUSIONS: TVV+CAIV-T appeared more immunogenic than TVV+P, but the observed difference may be clinically unimportant. Anti-influenza serum and nasal-wash antibodies were associated with immune protection.

• Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.

  Authors: Peter F Wright, Jiri Mestecky, M Juliana McElrath, Michael C Keefer, Geoffrey J Gorse, Paul A Goepfert, Zina Moldoveanu, David Schwartz, Paul W Spearman, Raphaelle El Habib, Michele D Spring, Yuwei Zhu, Carol Smith, Jorge Flores, Kent J Weinhold

  The Journal of infectious diseases. 05/2004; 189(7):1221-31.

  BACKGROUND: Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus-based vectors was conducted in 84BACKGROUND: Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus-based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. METHODS: Over the course of 6 months, HIV-1-specific (vCP 205) and rabies (vCP 65) canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. RESULTS: Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1-specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. CONCLUSIONS: Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen.

• Binding of antibodies to human immunodeficiency virus type 1 (HIV-1)-infected lymphocytes elicited by vaccines and by natural infection.

  Authors: Geoffrey J Gorse, Gira B Patel, J Alan Arbuckle, Robert B Belshe

  Vaccine. 02/2004; 22(3-4):383-97.

  Binding of antibodies to oligomeric envelope glycoprotein of R5-tropic primary isolates of human immunodeficiency virus type 1 (HIV-1) was studied by flow cytometry using sera from HIV-1 vaccineBinding of antibodies to oligomeric envelope glycoprotein of R5-tropic primary isolates of human immunodeficiency virus type 1 (HIV-1) was studied by flow cytometry using sera from HIV-1 vaccine recipients and clade B and C HIV-1-infected patients, and monoclonal and polyclonal antibodies to neutralizing epitopes of HIV-1. Vaccine recipients received recombinant canarypox virus vaccine expressing HIV-1 gene products, and SF-2 recombinant gp120 subunit vaccine. Anti-gp120 neutralizing antibodies including human monoclonal antibody 2G12 and goat polyclonal anti-serum to V3 loop peptide [peptide T1-SP10MN(A)] bound to HIV-1-infected cells. Sera from vaccine recipients bound to HIV-1-infected cells, but at levels lower than did infected patient sera.

• Efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a VA cooperative study.

  Authors: Geoffrey J Gorse, Theresa Z O'Connor, Stephen L Young, Paul M Mendelman, Suzanne F Bradley, Kristin L Nichol, James H Strickland, Daniel M Paulson, Kathryn L Rice, Runi A Foster, Ashok M Fulambarker, John W Shigeoka, Ware G Kuschner, Richard P Goodman, Kathleen M Neuzil, Janet Wittes, Kathy D Boardman, Peter N Peduzzi

  Vaccine. 06/2003; 21(17-18):2133-44.

  We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patientsWe assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subjects (N=2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): -0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: -0.17, 0.53), and -0.05 for type B virus (95% CL: -1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study.

• Recognizing influenza in older patients with chronic obstructive pulmonary disease who have received influenza vaccine.

  Authors: Kathleen M Neuzil, Theresa Z O'Connor, Geoffrey J Gorse, Kristin L Nichol

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 01/2003; 36(2):169-74.

  A substudy analysis was conducted to determine the clinical characteristics associated with symptomatic, laboratory-documented influenza (LDI) among 2215 veterans with chronic obstructive pulmonaryA substudy analysis was conducted to determine the clinical characteristics associated with symptomatic, laboratory-documented influenza (LDI) among 2215 veterans with chronic obstructive pulmonary disease who participated in Department of Veterans Affairs Cooperative Study 448 and who received trivalent inactivated influenza virus vaccine with or without intranasal live-attenuated, cold-adapted influenza vaccine. Of 585 evaluable first occurrences of acute respiratory illnesses, 94 (16%) were LDI. Respiratory symptoms of cough, sputum production, and dyspnea occurred in >90% of patients with LDI; 68% had documented or subjective fever, and 81% had myalgias. Stepwise logistic regression identified only fever and myalgia as being statistically associated with LDI. During the influenza outbreak period, the positive predictive value of fever and myalgia was 41%. Clinical criteria were poor predictors of LDI in these older, vaccinated patients with chronic lung disease. Additional studies are warranted to define optimal methods for the diagnosis of influenza among older persons with chronic obstructive pulmonary disease.

• Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A.

  Authors: Kalpana Gupta, Michael Hudgens, Lawrence Corey, M Juliana McElrath, Kent Weinhold, David C Montefiori, Geoffrey J Gorse, Sharon E Frey, Michael C Keefer, Thomas G Evans, Raphael Dolin, David H Schwartz, Clayton Harro, Barney Graham, Paul W Spearman, Mark Mulligan, Paul Goepfert

  Journal of acquired immune deficiency syndromes (1999). 04/2002; 29(3):254-61.

  To test the safety and immunogenicity of a high-titered preparation of ALVAC-HIV vCP205 in both high-risk and low-risk persons and to evaluate variations in dosing schedule, we conducted aTo test the safety and immunogenicity of a high-titered preparation of ALVAC-HIV vCP205 in both high-risk and low-risk persons and to evaluate variations in dosing schedule, we conducted a multicenter, randomized, double-blind trial of this vector in combination with recombinant subunit gp120 in 150 HIV-1-seronegative volunteers. The high-titered ALVAC vaccine was well tolerated; adverse events were minimal and not influenced by dosing. At day 728, the cumulative probability of a cytotoxic T-lymphocyte (CTL) response was 76% (95% confidence interval [CI]: 64%-89%) among volunteers receiving vaccine, and the net amount attributable to vaccination was 50% (CI: 16%; 74%). The net probability of a repeated positive CTL response by day 728 was 50% (CI: 21%; 64%). There was a significant difference in CTL response at day 182 between volunteers who had received four doses versus three doses of vCP205 (42% vs. 24%, p =.052). The CTL response was similar in high-risk volunteers and vaccinia-naive volunteers compared with vaccinia-immune volunteers. Neutralizing antibody responses were detected in 95% of vaccinees at day 287, with higher geometric mean titers in recipients of sequential versus simultaneous dosing of the two vaccines and in vaccinia-naive volunteers. This high-titered preparation of ALVAC-HIV vCP205 in combination with gp120 was safe and immunogenic in a diverse group of HIV-1-seronegative volunteers.

• Cytokine responses to human immunodeficiency virus type 1 (HIV-1) induced by immunization with live recombinant canarypox virus vaccine expressing HIV-1 genes boosted by HIV-1SF-2 recombinant GP120

  Authors: Geoffrey J. Gorse, Gira B. Patel, Mahendra D. Mandava, J.Alan Arbuckle, Timothy M. Doyle, Robert B. Belshe

  Vaccine.

  Vaccine-induced T-cell memory for human immunodeficiency virus type 1 (HIV-1) was assessed by measuring HIV-1 antigen-stimulated cytokine secretion in 72 HIV-1-uninfected subjects, of whom 52Vaccine-induced T-cell memory for human immunodeficiency virus type 1 (HIV-1) was assessed by measuring HIV-1 antigen-stimulated cytokine secretion in 72 HIV-1-uninfected subjects, of whom 52 received live recombinant canarypox virus vaccine expressing HIV-1 env, gag, and protease gene products (vCP205) with or without HIV-1SF-2 recombinant gp120 (SF-2 rgp120) subunit vaccine, and 20 the control. The vCP205 vaccine induced secretion of the Th1 cytokine, interferon-γ, by peripheral blood mononuclear cells (PBMC) after in vitro stimulation with HIV-1 p24 and envelope glycoprotein. Immunization schedules with both vCP205 and SF-2 rgp120 subunit vaccines induced secretion of Th1 and Th2 cytokines by PBMC to HIV-1 envelope glycoprotein. Hence, vCP205 and SF-2 rgp120 subunit vaccines given together and in a prime-boost sequence appeared to induce a broader cytokine response pattern than vCP205 vaccine given alone.

• Lymphocyte proliferative responses following immunization with human immunodeficiency virus recombinant GP160

  Authors: Geoffrey J. Gorse, Robert B. Belshe, Frances K. Newman, Sharon E. Frey, NIAID AIDS Vaccine Clinical Trials Network

  Vaccine.

  Following immunization of healthy adult volunteers with baculovirus-derived HIV-1 gp160 vaccine (rgp160), we measured lymphocyte proliferation to rgp160, the V3 loop peptide of gp160, controlFollowing immunization of healthy adult volunteers with baculovirus-derived HIV-1 gp160 vaccine (rgp160), we measured lymphocyte proliferation to rgp160, the V3 loop peptide of gp160, control proteins, and phytohaemagglutinin. Four persons received injections of 40 μg or 80 μg doses of rgp160 vaccine at times 0, and 1, 6 and 18 months; one additional volunteer received only three injections of vaccine. Vaccination with rgp160 induced lymphocyte proliferative responses to rgp160, but not to V3 loop peptide. Repeated injection of rgp160 even at low doses induced a cellular immune response which was not attributable to T-cell recognition of the V3 loop peptide.

• Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: A randomized, double-blinded, controlled, multicenter trial

  Authors: Geoffrey J. Gorse, Wendy Keitel, Harry Keyserling, David N. Taylor, Michael Lock, Katia Alves, Julie Kenner, Lynne Deans, Marc Gurwith

  Vaccine.

  BackgroundWe report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine.MethodsHundred healthy volunteers wereBackgroundWe report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine.MethodsHundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4.FindingsLocal reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p < 0.001) and the second (84.2% versus 35.4%; p < 0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively.InterpretationNo clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.

• HIV-1 recombinant gp160 vaccine induced antibodies in serum and saliva

  Authors: Geoffrey J. Gorse, Jason H. Rogers, John E. Perry, Frances D. Newman, Sharon E. Frey, Gira B. Patel, Robert B. Belshe, the NIAID AIDS Vaccine Clinical Trials Network

  Vaccine.

  As part of a phase I safety and immunogenicity trial of a vaccinia-expressed HIV-1 recombinant gp160 (rgp160) candidate vaccine, we measured serum and saliva antibody responses in low risk,As part of a phase I safety and immunogenicity trial of a vaccinia-expressed HIV-1 recombinant gp160 (rgp160) candidate vaccine, we measured serum and saliva antibody responses in low risk, uninfected volunteers. Six healthy adult volunteers received 50 μg doses of rgp160 vaccine adjuvanted in alum and deoxycholate at months 0, 1, 6, and 12. A 200 μg rgp160 immunization was given to four volunteers at 18 months. The vaccine induced anti-envelope glycoprotein IgG and IgA serum antibodies in all six volunteers. Saliva antibodies to envelope glycoprotein appeared in some volunteers at certain timepoints. Three volunteers appeared to transiently develop vaccine-induced secretory IgA antibody to envelope glycoprotein in whole saliva.