Immunomodulation for the Prevention and Treatment of Lung Infections

The clearance of microbes from the respiratory tract requires the generation of a vigorous and compartmentalized host immune response. When pulmonary infection occurs in the setting of impaired innate and acquired immune responses, antimicrobial agents alone often cannot cure the host. This article reviews both conventional and experimental approaches to stimulate innate and acquired immune responses. These strategies include immunotherapy to directly enhance effector cell function of phagocytic cells (e.g., cytokine immunotherapy) or skew immune responses toward protective type 1 immunity (e.g., CD40 ligand, CpG dinucleotides, cytokines). Additionally, the role of immunization (either active or passive) in the prevention and treatment of respiratory tract infection is addressed. Although the clinical context in which these immunomodulatory approaches may be of benefit in the treatment of respiratory tract infection remains uncertain, potential applications of immunotherapy are explored.

KEYWORDS

Immunotherapy - cytokines - pneumonia

REFERENCES

• 1 Davies J. Inactivation of antibiotics and dissemination of resistance genes.  Science. 1994;  264 375-382
• 2 Update C DC. Staphylococcus aureus resistant to vancomycin- United States, 2002.  MMWR Morb Mortal Wkly Rep. 2002;  51 565-567
• 3 Toews G B, Gross G N, Pierce A K. The relationship of inoculum size to lung bacterial clearance and phagocytic cell response in mice.  Am Rev Respir Dis. 1979;  120 559-566
• 4 Nelson S, Mason C M, Kolls J K. Pathophysiology of pneumonia.  Clin Chest Med. 1995;  16 1-12
• 5 Moore T A, Moore B, Standiford T J. Gamma delta T cells are required for protective innate immune responses in murine Klebsiella pneumonia.  J Immunol. 2000;  165 2643-2650
• 6 Malaviya R, Ikeda T, Ross E, Abraham S N. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha.  Nature. 1996;  2 381:21-22
• 7 Standiford T J, Huffnagle G B. Cytokines in host defense against pneumonia.  J Invest Med. 1997;  45 335-345
• 8 Reddy R C, Chen G H, Tekchandana P K, Standiford T J. Sepsis-induced immunosuppression.  Immunol Res. 2001;  24 273-287
• 9 Volk H D, Reinke P, Docke W D. Clinical aspects: from systemic inflammation to “immunoparalysis”.  Chem Immunol. 2000;  74 162-177
• 10 Appel S H, Wellhausen S R, Montgomery R et al.. Experimental and clinical significance of endotoxin-dependent HLA-DR expression on monocytes.  J Surg Res. 1989;  47 39-44
• 11 Munoz C, Carlet J, Fitting C et al.. Dysregulation of in vitro cytokine production by monocytes during sepsis.  J Clin Invest. 1991;  88 1747-1754
• 12 Tracey K J, Beutler B, Lowry S F, Cerami A. Shock and tissue injury induced by recombinant human cachectin.  Science. 1986;  234 470-474
• 13 News and Comment . IL-12 deaths: explanation and the puzzle.  Science. 1995;  270 908
• 14 Wilson J M. Molecular medicine: adenoviruses as gene-delivery vehicles.  N Engl J Med. 1996;  334 1185-1187
• 15 Roilides E, Walsh T J, Pizzo P A et al.. G-CSF enhances the phagocytic and bactericidal activity of normal and defective human neutrophils.  J Infect Dis. 1991;  163 579-583
• 16 Hebert J C, O'Reilly M, Gamelli R L. Protective effect of recombinant human granulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice.  Arch Surg. 1990;  125 1075-1078
• 17 Nelson S, Summer W, Bagby G et al.. Granulocyte colony-stimuating factor enhances pulmonary host defenses in normal and ethanol-treated rats.  J Infect Dis. 1991;  164 901-906
• 18 Smith W S, Sumnicht G E, Sharpe R W, Samuelson D, Millard F E. Granulocyte colony-stimulating factor versus placebo in addition to penicillin G in randomized blinded study of gram-negative pneumonia sepsis: analysis of survival and multisystem organ failure.  Blood. 1995;  86 1301-1309
• 19 Dierdorf R, Kreuter U, Jones T C. A role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of neutropenic patients with pneumonia.  Braz J Infect Dis. 1997;  1 68-76
• 20 Keiser P, Rademacher S, Smith J W et al.. Granulocyte colony-stimulating factor use is associated with decreased bacteremia and increased survival in neutropenic HIV-infected patients.  Am J Med. 1998;  104 48-55
• 21 Gruson D, Hilbert G, Vargas F et al.. Impact of colony-stimulating factor therapy on clinical outcome and frequency rate of nosocomial infections in intensive care unit neutropenic patients.  Crit Care Med. 2000;  28 3155-3160
• 22 Nelson S, Belnap S M, Carlson R W et al.. A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia.  J Infect Dis. 1998;  178 1075-1080
• 23 Nelson S, Heyder A M, Stone J et al.. A randomized controlled trial of filgrastim for the treatment of hospitalized patients with multilobar pneumonia.  J Infect Dis. 2000;  182 970-973
• 24 Wunderink R G, Leeper Jr K V, Schein R et al.. Filgrastim in patients with pneumonia and severe sepsis or septic shock.  Chest. 2001;  119 523-529
• 25 Berclaz P-Y, Shibata Y, Whitsett J A, Trapnell B C. GM-CSF, via PU.1, regulates alveolar macrophage FcγR-mediated phagocytosis and the IL-18/IFN-γ-mediated molecular connection between innate and adaptive immunity in the lung.  Blood. 2002;  100 4193-4200
• 26 Levine A M, Reed J A, Kurak K E, Cianciolo E, Whisett J A. GM-CSF deficient mice are susceptible to pulmonary group B streptococcal infection.  J Clin Invest. 1999;  103 563-569
• 27 Paine III R, Preston A M, Wilcoxen S et al.. Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice.  J Immunol. 2000;  164 2602-2609
• 28 Manfredi R, Mastroianni M R, Coronado O, Chiodo F. Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in leukopenic patients with advanced HIV disease.  J Chemother. 1996;  8 214-220
• 29 Hebert J C, O'Reilly M. Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances pulmonary defenses against pneumococcal infections after splenectomy.  J Trauma. 1996;  41 663-666
• 30 Nierhaus A, Montag B, Timmler N et al.. Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis.  Intensive Care Med. 2003;  29 646-651
• 31 Presneill J J, Harris T, Stewart A et al.. A randomized phase II trail of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction.  Am J Respir Crit Care Med. 2002;  166 138-143
• 32 Jenson W, Rose R, Wasserman A, Kalb T, Anton K, Remold H. In vitro activation of the antibacterial activity of human pulmonary macrophages by recombinant gamma interferon.  J Infect Dis. 1987;  155 574-577
• 33 Ahlin A, Elinder G, Palmblad J. Dose-dependent enhancements by interferon-gamma on functional responses of neutrophils from chronic granulomatous disease patients.  Blood. 1997;  89 3396-3401
• 34 Rubins J B, Pomeroy C. Role of gamma interferon in the pathogenesis of bacteremic pneumococcal pneumonia.  Infect Immun. 1997;  65 2975-2977
• 35 Newport M J, Huxley C M, Huston S et al.. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection.  N Engl J Med. 1996;  335 1941-1949
• 36 Jounanguy E, Altare F, Lamhamedi S et al.. Interferon-gamma receptor deficiency in an infant with fatal bacilli Calmette-Guérin infection.  N Engl J Med. 1996;  335 1956-1961
• 37 Beck J, Liggitt H, Brunette E, Fuchs H, Shellito J, Debs R. Reduction in intensity of Pneumocystis carinii pneumonia in mice by aerosol administration of gamma interferon.  Infect Immun. 1991;  59 3859-3862
• 38 Skerrett S, Martin T. Intratracheal interferon-γ augments pulmonary defenses in experimental legionellosis.  Am J Respir Crit Care Med. 1994;  149 50-58
• 39 Lei D, Lancaster J R, Joshi M S et al.. Activation of alveolar macrophages and lung host defenses using transfer of the interferon-gamma gene.  Am J Physiol. 1997;  272 L852-L859
• 40 Deng J, Tateda K, Zeng X, Standiford T J. Transient transgenic expression of IFN-γ promotes Legionella pneumophila clearance in immunocompetent hosts.  Infect Immun. 2001;  69 6382-6390
• 41 Johnston Jr R B. Clinical aspects of chronic granulomatous disease.  Curr Opin Hematol. 2001;  8 17-22
• 42 Conte D, Fraquelli M, Capsoni F et al.. Effectiveness of IFN-gamma for liver abscesses in chronic granulomatous disease.  J Interferon Cytokine Res. 1999;  19 705-710
• 43 Docke W D, Randow F, Syrbe U et al.. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment.  Nat Med. 1997;  3 678-681
• 44 Honore I, Nunes H, Groussard O et al.. Acute respiratory failure after interferon-gamma therapy of end-stage pulmonary fibrosis.  Am J Respir Crit Care Med. 2003;  167 953-957
• 45 Brunda M. Interleukin-12.  J Leukoc Biol. 1994;  55 280-288
• 46 Chehimi J, Trinchieri G. Interleukin-12: a bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency.  J Clin Immunol. 1994;  14 149-159
• 47 Greenberger M J, Kunkel S L, Strieter R M et al.. IL-12 gene therapy protects mice in lethal Klebsiella pneumonia.  J Immunol. 1996;  157 3006-3012
• 48 deJong R, Altare F, Haagen I A et al.. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.  Science. 1998;  280 1435-1438
• 49 Flynn J L, Goldstein M M, Triebold K J, Sypek J, Wolf S, Bloom B R. IL-12 increases resistance of BALB/c mice to Mycobacterium tuberculosis infection.  J Immunol. 1995;  155 2515-2524
• 50 Kawakami K, Tohyama M, Xie Q, Saito A. IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans .  Clin Exp Immunol. 1996;  104 208-214
• 51 O'Brien C B, Moonka D K, Henzel B S et al.. A pilot trial of recombinant interleukin-12 in patients with chronic hepatitis C who previously failed treatment with interferon-alpha.  Am J Gastroenterol. 2001;  96 2473-2479
• 52 Jacobson M A, Spritzler J, Landay A et al.. A phase 1, placebo-controlled trial of multi-dose recombinant human interleukin-12 in patients with HIV infection.  AIDS. 2002;  16 1147-1154
• 53 Rolph P, Nakoinz I, Sampson-Johannes A et al.. IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor.  J Immunol. 1992;  148 808-814
• 54 Howard M, O'Garra A, Ishida H, Malefyt R D, De Vries J. Biological properties of interleukin 10.  J Clin Immunol. 1992;  12 239-247
• 55 Howard M, Muchamuel T, Andrade S, Menon S. Interleukin 10 protects mice from lethal endotoxemia.  J Exp Med. 1993;  177 1205-1208
• 56 Standiford T J, Strieter R M, Lukacs N W, Kunkel S L. Neutralization of IL-10 increases lethality in endotoxemia: cooperative effects of macrophage inflammatory protein-2 and tumor necrosis factor.  J Immunol. 1995;  155 2222-2229
• 57 Bermudez L E, Champsi J. Infection with Mycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice.  Infect Immun. 1993;  61 3093-3097
• 58 Greenberger M J, Strieter R M, Kunkel S L, Danforth J, Goodman R, Standiford T J. Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia.  J Immunol. 1995;  155 722-729
• 59 van der Poll T, Marchant A, Keogh C, Goldman M, Lowry S. Interleukin-10 impairs host defense in murine pneumococcal pneumonia.  J Infect Dis. 1996;  174 994-1000
• 60 Steinhauser M L, Hogboam C M, Kunkel S L, Lukacs N, Strieter R M, Standiford T J. IL-10 is a major mediator of sepsis-induced impairment in lung antibacterial host defense.  J Immunol. 1999;  162 392-399
• 61 Sawa T, Corry D B, Gropper M A, Ohara M, Kurahashi K, Wiener-Kronish J P. IL-10 improves lung injury and survival in Pseudomonas aeruginosa pneumonia.  J Immunol. 1997;  159 2858-2866
• 62 Morrison D F, Foss D L, Murtaugh M P. Interleukin-10 gene therapy amelioration of bacterial pneumonia.  Infect Immun. 2000;  68 4752-4758
• 63 Qureshi M H, Harmsen A G, Garvy B A. IL-10 modulates host responses and lung damage induced by Pneumocystis carinii infection.  J Immunol. 2003;  170 1002-1009
• 64 MacFadden D K, Edelson J D, Hyland R H, Rodriquez C H, Inouye T, Rebuck A S. Corticosteroids as adjuvant therapy in the treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.  Lancet. 1987;  1 1477-1479
• 65 Laman J D, Claasen E, Noelle R J. Functions of CD40 and its ligand, gp39 (CD40L).  Crit Rev Immunol. 1996;  16 59-70
• 66 Borrow P, Tishon A, Lee S et al.. CD40L-deficient mice show defects in antiviral immunity and have an impaired memory CD8⁺ CTL response.  J Exp Med. 1996;  183 2129-2137
• 67 Oz H S, Hughes W T, Rehg J E, Thomas E K. Effect of CD40 ligand and other immunomodulators on Pneumocystis carinii infection in rat model.  Microb Pathog. 2000;  29 187-190
• 68 Tripp R A, Jones L, Anderson L J, Brown M P. CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratory synctial virus in the BALB/c mouse.  J Immunol. 2000;  164 5913-5921
• 69 Kikuchi T, Hackett N R, Crystal R G. Cross-strain protection against clinical and laboratory strains of Pseudomonas aeruginosa mediated by dendritic cells genetically modified to express CD40 ligand and pulsed with specific strains of Pseudomonas aeruginosa .  Hum Gene Ther. 2001;  12 1251-1263
• 70 Kikuchi T, Worgall S, Singh R et al.. Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4⁺ T cells.  Nat Med. 2000;  6 1154-1159
• 71 Zheng M, Shellito J E, Marrero L et al.. CD4+ cell-independent vaccination against Pneumocystis carinii in mice.  J Clin Invest. 2001;  108 1469-1474
• 72 Krieg A. The role of CpG motifs in innate immunity.  Curr Opin Immunol. 2000;  12 35-43
• 73 Hayashi T, Rao S P, Takabayashi K et al.. Enhancement of innate immunity against Mycobacterium avium infection by immunostimulatory DNA is mediated by indoleamine 2,-dioxygenase.  Infect Immun. 2001;  69 6156-6164
• 74 Freidag B L, Melton G B, Collins F et al.. CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M. tuberculosis .  Infect Immun. 2000;  68 2948-2953
• 75 Pal S, Davis H L, Peterson E M, de la Maza L M. Immunization with the Chlamydia trachomatis mouse pneumonitis major outer membrane protein by use of CpG oligodeoxynucleotides as an adjuvant induces a protective immune response against an intranasal chlamydial challenge.  Infect Immun. 2002;  70 4812-4817
• 76 Hancock G E, Heers K M, Smith J D et al.. CpG containing oligodeoxynucleotides are potent adjuvants for parenteral vaccination with the fusion (F) protein of respiratory syncytial virus (RSV).  Vaccine. 2001;  19 4874-4882
• 77 Rose S C, McCool T, Greenspan N S et al.. CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies.  Infect Immun. 2000;  68 1450-1456
• 78 Gross P A. Vaccines for pneumonia and new antiviral therapies.  Med Clin North Am. 2001;  85 1531-1544
• 79 Eskola J, Antitila M. Pneumococcal conjugate vaccines.  Pediatr Infect Dis J. 1999;  18 543-551
• 80 Fedson D S, Wajda A, Nicol P et al.. Clinical effectiveness of influenza vaccination in Manitoba.  JAMA. 1993;  270 1956-1961
• 81 Nichol K L, Margolis K L, Wuorenma J et al.. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community.  N Engl J Med. 1994;  331 778-784
• 82 Singh M, O'Hagan D. Advances in vaccine adjuvants.  Nat Biotechnol. 1999;  17 1075-1081
• 83 Shinefield H, Black S, Fattom A et al.. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis.  N Engl J Med. 2002;  346 491-496
• 84 Trolle S, Chachaty E, Kassis-Chikhani N et al.. Intranasal immunization with protein-linked phosphorylcholine protects mice against a lethal intranasal challenge with Streptococcus pneumonia.  Vaccine. 2000;  18 2991-2998
• 85 Cahill E, O'Hagan D, Illum L et al.. Immune responses and protection against Bordetella pertussis infection after intranasal immunization of mice with filamentous haemagglutinin in solution or incorporated in biodegradable microparticles.  Vaccine. 1995;  13 455-462
• 86 Prideaux C T, Lenghaus C, Krywult J et al.. Vaccination and protection of pigs against pleuropneumonia with a vaccine-strain of Actinobacillus pleuropneumoniae produced by site-specific mutagenesis of the ApxII peron.  Infect Immun. 1999;  67 1962-1966
• 87 Bandholtz L, Kreuger M R, Svanholm C, Wigzell H, Rottenberg M E. Adjuvant modulation of the immune responses and the outcome of infection with Chlamydia pneumoniae .  Clin Exp Immunol. 2002;  130 393-403
• 88 Pascale J M, Shaw M M, Durant P J et al.. Intranasal immunization confers protection against murine Pneumocystis carinii lung infection.  Infect Immun. 1999;  67 805-809
• 89 Mallett C P, Hale T L, Kaminski R W et al.. Intranasal or intragastric immunization with proteosome-Shigella lipopolysaccharide vaccines protects against lethal pneumonia in a murine model of Shigella infection.  Infect Immun. 1995;  63 2382-2386
• 90 Shahin R, Leef M, Eldridge J, Hudson M, Gilley R. Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly (DL-lactide-co-glycolide) microspheres.  Infect Immun. 1995;  63 1195-1200
• 91 Nichol K L, Mendelman P M, Mallon K P et al.. Effectiveness of live, attenuated intranasal influenzavirus vaccine in healthy working adults.  JAMA. 1999;  282 137-144
• 92 McDonnell W M, Askari F K. Molecular medicine: DNA vaccines.  N Engl J Med. 1996;  334 42-45
• 93 Penttila T, Vuola J M, Puurula V et al.. Immunity to Chlamydia pneumoniae induced by vaccination with DNA vectors expressing a cytoplasmic protein (Hsp60) or outer membrane proteins (MOMP and Omp2).  Vaccine. 2000;  19 1256-1265
• 94 Zhang D, Yang X, Berry J et al.. DNA vaccination with the major outer-membrane protein gene induces acquired immunity to Chlamydia trachomatis (mouse pneumonitis) infection.  J Infect Dis. 1997;  176 1035-1040
• 95 Lai W C, Pakes S P, Ren K et al.. Therapeutic effect of DNA immunization of genetically susceptible mice infected with virulent Mycoplasma pulmonis .  J Immunol. 1997;  158 2513-2516
• 96 Chen Y-L, Wang S-N, Yang W-J et al.. Expression and immunogenicity of Mycoplasma hyopneumoniae heat shock protein antigen P42 by DNA vaccination.  Infect Immun. 2003;  71 1155-1160
• 97 Chen Y, Webster R G, Woodland D L. Induction of CD8⁺ T cell responses to dominant and subdominant epitopes and protective immunity to Sendai virus infection by DNA vaccination.  J Immunol. 1998;  160 2425-2432
• 98 Tascon R E, Colston M J, Ragno S et al.. Vaccination against tuberculosis by DNA injection.  Nat Med. 1996;  2 888-892
• 99 Svanholm C, Bandholtz L, Castanos-Velez E et al.. Protective DNA immunization against Chlamydia pneumoniae .  Scand J Immunol. 2000;  51 345-353
• 100 Okada E, Sasaki S, Ishii N et al.. Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens.  J Immunol. 1997;  159 3638-3647
• 101 Polack F P, Lee S H, Permar S et al.. Successful DNA immunization against measles: neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles.  Nat Med. 2000;  6 776-781
• 102 Skerrett S J. Antibody treatment of lower respiratory tract infections.  Semin Respir Infect. 2001;  16 67-75
• 103 Rosen F S, Cooper M D, Wedgewood R J. The primary immunodeficiencies.  N Engl J Med. 1995;  333 431-440
• 104 Buckley R H, Schiff R I. The use of intravenous immune globulin in immunodeficiency diseases.  N Engl J Med. 1991;  325 110-117
• 105 deHennezel L, Ramisse F, Binder P et al.. Effective combination therapy for invasive Pneumococcal pneumonia with ampicillin and intravenous immunoglobulins in a mouse model.  Antimicrob Agents Chemother. 2001;  45 316-318
• 106 Landsperger W J, Kelly-Wintenberg K D, Montie T C et al.. Inhibition of bacterial motility with human antiflagellar monoclonal antibodies attenuates Pseudomonas aeruginosa-induced pneumonia in the immunocompetent rat.  Infect Immun. 1994;  62 4825-4830
• 107 Saravolatz L D, Markowitz N, Collins M S, Bogdanoff D, Pennington J E. Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and non-septic patients.  J Infect Dis. 1991;  164 803-806
• 108 Glass I, Schorer R. Adjuvant therapy with Pseudomonas immunoglobulin in artificially ventilated patients at a surgery intensive care unit.  Anaesth Intensive Care. 1989;  24 167-171
• 109 Cometta A, Baumgartner J-D, Lee M L et al.. Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection.  N Engl J Med. 1992;  327 234-240
• 110 Just H M, Metzger M, Vogel W et al.. Effect of adjuvant immunoglobulin therapy on infections in patients in a surgical intensive care unit: results of a randomized controlled study.  Klin Wochenschr. 1986;  64 245-256
• 111 de Simone C, Delogu G, Corbetta G. Intravenous immunoglobulins in association with antibiotics: a therapeutic trial in septic intensive care unit patients.  Crit Care Med. 1988;  16 23-26
• 112 Dominioni L, Dionigi R, Zanello M et al.. Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater.  Arch Surg. 1991;  126 236-240
• 113 Harrison F J, Rohm D, Kohzuki T et al.. Pharmacokinetics, tolerability, and preliminary efficacy of human anti-Pseudomonas aeruginosa monoclonal antibodies in pneumonia and burn infection patients.  Hybridoma. 1997;  16 413-420
• 114 Comette A, Baumgartner J D, Glauser M P. Polyclonal intravenous immune globulin for prevention and treatment of infections in critically ill patients.  Clin Exp Immunol. 1994;  97 69-72
• 115 Kelly J. Immunotherapy against antibiotic-resistant bacteria: the Russian experience with an antistaphylococcal hyperimmune plasma and immunoglobulin.  Microbes Infect. 2000;  2 1383-1392
• 116 Reed E C, Bowden R A, Dandliker P S et al.. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants.  Ann Intern Med. 1988;  109 783-788
• 117 Whimbley E, Champlin R E, England J A et al.. Combination therapy with aerosolized ribavivrin and intravenous immunoglobulin for respiratory syncytial virus disease in adult bone marrow transplant recipients.  Bone Marrow Transplant. 1995;  16 393-399
• 118 Casadevall A, Feldmesser M, Pirofski L A. Induced humoral immunity and vaccination against major human fungal pathogens.  Curr Opin Microbiol. 2002;  5 386-391
• 119 Gigliotti F, Haidaris G C, Wright T W, Harmsen A G. Passive intranasal monoclonal antibody prophylaxis against murine Pneumocystis carinii pneumonia.  Infect Immun. 2002;  70 1069-1074
• 120 Ramisse F, Binder P, Szatanik M et al.. Passive and active immunotherapy for experimental pneumococcal pneumonia by polyvalent human immunoglobulin or F(ab′)2 fragments administered intranasally.  J Infect Dis. 1996;  173 1123-1128