Progress in Respiratory Virus Vaccine Development

ABSTRACT

Viral respiratory infections continue to cause significant morbidity and mortality in infants and young children as well as in at-risk adults and the elderly. Although many viral pathogens are capable of causing acute respiratory disease, vaccine development has to focus on a limited number of pathogens (i.e., agents that commonly cause serious lower respiratory disease). Inactivated and, more recently, live attenuated influenza virus vaccines are the mainstay of interpandemic influenza prevention, but vaccines are not available yet for other important viruses such as respiratory syncytial virus, metapneumovirus, the parainfluenza viruses, and avian influenza viruses with pandemic potential. Reverse genetics systems that allow rational vaccine development are now widely used, and considerable progress has been made in preclinical and clinical development of novel respiratory virus vaccines.

KEYWORDS

Vaccine - influenza virus - parainfluenza virus - metapneumovirus - respiratory syncytial virus - clinical trial

REFERENCES

• 1 The World Health Report: 2005: Make Every Mother and Child Count. Geneva: WHO; 2005
• 2 Falsey A R, Hennessey P A, Formica M A, Cox C, Walsh E E. Respiratory syncytial virus infection in elderly and high-risk adults.  N Engl J Med. 2005;  352 1749-1759
• 3 Falsey A R, Formica M A, Hennessey P A, Criddle M M, Sullender W M, Walsh E E. Detection of respiratory syncytial virus in adults with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2006;  173 639-643
• 4 Thompson W W, Shay D K, Weintraub E et al.. Mortality associated with influenza and respiratory syncytial virus in the United States.  JAMA. 2003;  289 179-186
• 5 Falsey A R, Walsh E E. Viral pneumonia in older adults.  Clin Infect Dis. 2006;  42 518-524
• 6 Subbarao K, Roberts A. Is there an ideal animal model for SARS?.  Trends Microbiol. 2006;  14 299-303
• 7 Stadler K, Rappuoli R. SARS: understanding the virus and development of rational therapy.  Curr Mol Med. 2005;  5 677-697
• 8 Gray G C, Goswami P R, Malasig M D et al.. Adult adenovirus infections: loss of orphaned vaccines precipitates military respiratory disease epidemics.  Clin Infect Dis. 2000;  31 663-670
• 9 Spier R E. On the need for, and the delivery of, cross-protective vaccines.  Vaccine. 2005;  23 2027-2029
• 10 Wilson J, Rowlands K, Rockett K et al.. Genetic variation at the IL10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis.  J Infect Dis. 2005;  191 1705-1709
• 11 Crowe Jr J E, Williams J V. Immunology of viral respiratory tract infection in infancy.  Paediatr Respir Rev. 2003;  4 112-119
• 12 Guarner J, Paddock C D, Shieh W J et al.. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season.  Clin Infect Dis. 2006;  43 132-140
• 13 Zhang L, Peeples M E, Boucher R C, Collins P L, Pickles R J. Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology.  J Virol. 2002;  76 5654-5666
• 14 Collins P L, Chanock R M, Murphy B R. Respiratory syncytial virus. In: Knipe DM, Howley PM, Griffin DE, et al Fields Virology. Vol 1. 4th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 1443-1486
• 15 Collins P L, Murphy B R. New generation live vaccines against human respiratory syncytial virus designed by reverse genetics.  Proc Am Thorac Soc. 2005;  2 166-173
• 16 Lemanske R F. Viral infections and asthma inception.  J Allergy Clin Immunol. 2004;  114 1023-1026
• 17 Everard M L. The relationship between respiratory syncytial virus infections and the development of wheezing and asthma in children.  Curr Opin Allergy Clin Immunol. 2006;  6 56-61
• 18 Psarras S, Papadopoulos N G, Johnston S L. Pathogenesis of respiratory syncytial virus bronchiolitis-related wheezing.  Paediatr Respir Rev. 2004;  5(Suppl A) S179-S184
• 19 Hacking D, Hull J. Respiratory syncytial virus-viral biology and the host response.  J Infect. 2002;  45 18-24
• 20 Puthothu B, Krueger M, Forster J, Heinzmann A. Association between severe respiratory syncytial virus infection and IL13/IL4 haplotypes.  J Infect Dis. 2006;  193 438-441
• 21 Hoebee B, Bont L, Rietveld E et al.. Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.  J Infect Dis. 2004;  189 239-247
• 22 Mills J, Van Kirk J E, Wright P F, Chanock R M. Experimental respiratory syncytial virus infection of adults: possible mechanisms of resistance to infection and illness.  J Immunol. 1971;  107 123-130
• 23 Watt P J, Robinson B S, Pringle C R, Tyrrell D A. Determinants of susceptibility to challenge and the antibody response of adult volunteers given experimental respiratory syncytial virus vaccines.  Vaccine. 1990;  8 231-236
• 24 Kulkarni A B, Collins P L, Bacik I et al.. Cytotoxic T cells specific for a single peptide on the M2 protein of respiratory syncytial virus are the sole mediators of resistance induced by immunization with M2 encoded by a recombinant vaccinia virus.  J Virol. 1995;  69 1261-1264
• 25 Plotnicky-Gilquin H, Robert A, Chevalet L et al.. CD4(+) T-cell-mediated antiviral protection of the upper respiratory tract in BALB/c mice following parenteral immunization with a recombinant respiratory syncytial virus G protein fragment.  J Virol. 2000;  74 3455-3463
• 26 Plotnicky-Gilquin H, Cyblat-Chanal D, Aubry J P et al.. Gamma interferon-dependent protection of the mouse upper respiratory tract following parenteral immunization with a respiratory syncytial virus G protein fragment.  J Virol. 2002;  76 10203-10210
• 27 Group TI-RS . Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants.  Pediatrics. 1998;  102(3 Pt 1) 531-537
• 28 Crowe Jr J E. Influence of maternal antibodies on neonatal immunization against respiratory viruses.  Clin Infect Dis. 2001;  33 1720-1727
• 29 Crowe Jr J E, Firestone C Y, Murphy B R. Passively acquired antibodies suppress humoral but not cell-mediated immunity in mice immunized with live attenuated respiratory syncytial virus vaccines.  J Immunol. 2001;  167 3910-3918
• 30 Karron R A, Wright P F, Belshe R B et al.. Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants.  J Infect Dis. 2005;  191 1093-1104
• 31 Nolan S M, Surman S R, Amaro-Carambot E, Collins P L, Murphy B R, Skiadopoulos M H. Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses.  Vaccine. 2005;  23 4765-4774
• 32 McAuliffe J M, Surman S R, Newman J T et al.. Codon substitution mutations at two positions in the L polymerase protein of human parainfluenza virus type 1 yield viruses with a spectrum of attenuation in vivo and increased phenotypic stability in vitro.  J Virol. 2004;  78 2029-2036
• 33 Bukreyev A, Belyakov I M, Berzofsky J A, Murphy B R, Collins P L. Granulocyte-macrophage colony-stimulating factor expressed by recombinant respiratory syncytial virus attenuates viral replication and increases the level of pulmonary antigen-presenting cells.  J Virol. 2001;  75 12128-12140
• 34 Bukreyev A, Skiadopoulos M H, McAuliffe J, Murphy B R, Collins P L, Schmidt A C. More antibody with less antigen: can immunogenicity of attenuated live virus vaccines be improved?.  Proc Natl Acad Sci USA. 2002;  99 16987-16991
• 35 Schmidt A C, Wenzke D R, McAuliffe J M et al.. Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.  J Virol. 2002;  76 1089-1099
• 36 Kim H W, Canchola J G, Brandt C D et al.. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine.  Am J Epidemiol. 1969;  89 422-434
• 37 Piedra P A. Clinical experience with respiratory syncytial virus vaccines.  Pediatr Infect Dis J. 2003;  22(Suppl 2) S94-S99
• 38 Kneyber M C, Kimpen J L. Advances in respiratory syncytial virus vaccine development.  Curr Opin Investig Drugs. 2004;  5 163-170
• 39 Johnson T R, Graham B S. Contribution of respiratory syncytial virus G antigenicity to vaccine-enhanced illness and the implications for severe disease during primary respiratory syncytial virus infection.  Pediatr Infect Dis J. 2004;  23(Suppl 1) S46-S57
• 40 Openshaw P J, Culley F J, Olszewska W. Immunopathogenesis of vaccine-enhanced RSV disease.  Vaccine. 2001;  20(Suppl 1) S27-S31
• 41 Piedra P A, Cron S G, Jewell A et al.. Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: a multi-center trial in children with cystic fibrosis.  Vaccine. 2003;  21 2448-2460
• 42 Munoz F M, Piedra P A, Glezen W P. Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women.  Vaccine. 2003;  21 3465-3467
• 43 Ison M G, Johnston S L, Openshaw P, Murphy B, Hayden F. Current research on respiratory viral infections: Fifth International Symposium.  Antiviral Res. 2004;  62 75-110
• 44 Wright P F, Karron R A, Madhi S A et al.. The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans.  J Infect Dis. 2006;  193 573-581
• 45 Wright P F, Karron R A, Belshe R B et al.. Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy.  J Infect Dis. 2000;  182 1331-1342
• 46 Biacchesi S, Skiadopoulos M H, Yang L et al.. Recombinant human metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate.  J Virol. 2004;  78 12877-12887
• 47 Biacchesi S, Pham Q N, Skiadopoulos M H, Murphy B R, Collins P L, Buchholz U J. Infection of nonhuman primates with recombinant human metapneumovirus lacking the SH, G, or M2-2 protein categorizes each as a nonessential accessory protein and identifies vaccine candidates.  J Virol. 2005;  79 12608-12613
• 48 Buchholz U J, Biacchesi S, Pham Q N et al.. Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus: effects on RNA synthesis, attenuation, and immunogenicity.  J Virol. 2005;  79 6588-6597
• 49 Pham Q N, Biacchesi S, Skiadopoulos M H, Murphy B R, Collins P L, Buchholz U J. Chimeric recombinant human metapneumoviruses with the nucleoprotein or phosphoprotein open reading frame replaced by that of avian metapneumovirus exhibit improved growth in vitro and attenuation in vivo.  J Virol. 2005;  79 15114-15122
• 50 Skiadopoulos M H, Surman S, Tatem J M et al.. Identification of mutations contributing to the temperature-sensitive, cold-adapted, and attenuation phenotypes of the live-attenuated cold-passage 45 (cp45) human parainfluenza virus 3 candidate vaccine.  J Virol. 1999;  73 1374-1381
• 51 Karron R A, Belshe R B, Wright P F et al.. A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants.  Pediatr Infect Dis J. 2003;  22 394-405
• 52 Belshe R B, Newman F K, Tsai T F et al.. Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old.  J Infect Dis. 2004;  189 462-470
• 53 Belshe R B, Newman F K, Anderson E L et al.. Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children.  J Infect Dis. 2004;  190 2096-2103
• 54 van Wyke Coelingh K L, Winter C C, Tierney E L, London W T, Murphy B R. Attenuation of bovine parainfluenza virus type 3 in nonhuman primates and its ability to confer immunity to human parainfluenza virus type 3 challenge.  J Infect Dis. 1988;  157 655-662
• 55 Karron R A, Makhene M, Gay K, Wilson M H, Clements M L, Murphy B R. Evaluation of a live attenuated bovine parainfluenza type 3 vaccine in two- to six-month-old infants.  Pediatr Infect Dis J. 1996;  15 650-654
• 56 Greenberg D P, Walker R E, Lee M S et al.. A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy.  J Infect Dis. 2005;  191 1116-1122
• 57 Schmidt A C, McAuliffe J M, Huang A et al.. Bovine parainfluenza virus type 3 (BPIV3) fusion and hemagglutinin-neuraminidase glycoproteins make an important contribution to the restricted replication of BPIV3 in primates.  J Virol. 2000;  74 8922-8929
• 58 Newman J T, Riggs J M, Surman S R et al.. Generation of recombinant human parainfluenza virus type 1 vaccine candidates by importation of temperature-sensitive and attenuating mutations from heterologous paramyxoviruses.  J Virol. 2004;  78 2017-2028
• 59 Bartlett E J, Amaro-Carambot E, Surman S R, Collins P L, Murphy B R, Skiadopoulos M H. Introducing point and deletion mutations into the P/C gene of human parainfluenza virus type 1 (HPIV1) by reverse genetics generates attenuated and efficacious vaccine candidates.  Vaccine. 2006;  24 2674-2684
• 60 Bartlett E J, Amaro-Carambot E, Surman S R et al.. Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys.  Vaccine. 2005;  23 4631-4646
• 61 Van Cleve W, Amaro-Carambot E, Surman S R et al.. Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1.  Virology. 2006;  352 61-73
• 62 Belshe R B, Gruber W C, Mendelman P M et al.. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.  J Pediatr. 2000;  136 168-175
• 63 Belshe R, Lee M S, Walker R E, Stoddard J, Mendelman P M. Safety, immunogenicity and efficacy of intranasal, live attenuated influenza vaccine.  Expert Rev Vaccines. 2004;  3 643-654
• 64 Belshe R B, Mendelman P M, Treanor J et al.. The efficacy of live attenuated, cold-adapted, trivalent, intranasal Influenzavirus vaccine in children.  N Engl J Med. 1998;  338 1405-1412
• 65 Stephenson I, Gust I, Pervikov Y, Kieny M P. Development of vaccines against influenza H5.  Lancet Infect Dis. 2006;  6 458-460
• 66 Luke C J, Subbarao K. Vaccines for pandemic influenza.  Emerg Infect Dis. 2006;  12 66-72
• 67 Stephenson I, Nicholson K G, Wood J M, Zambon M C, Katz J M. Confronting the avian influenza threat: vaccine development for a potential pandemic.  Lancet Infect Dis. 2004;  4 499-509
• 68 Fauci A S. Pandemic influenza threat and preparedness.  Emerg Infect Dis. 2006;  12 73-77
• 69 Palese P. Making better influenza virus vaccines?.  Emerg Infect Dis. 2006;  12 61-65
• 70 Treanor J J, Campbell J D, Zangwill K M, Rowe T, Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine.  N Engl J Med. 2006;  354 1343-1351
• 71 Bresson J L, Perronne C, Launay O et al.. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial.  Lancet. 2006;  367 1657-1664
• 72 Chen H, Matsuoka Y, Swayne D et al.. Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza virus vaccine candidate.  Vaccine. 2003;  21 4430-4436
• 73 Karron R. Phase I Inpatient Evaluation of a Live Attenuated H9N2 ca Reassortant Vaccine in Healthy Adults Born after 1968. 2005 http://Accessed 09/20/2006: www.who.int/vaccine_research/diseases/influenza/mtg_021205/en/index3.html
• 74 Suguitan A L, McAuliffe J, Mills K L et al.. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.  PLoS Med. 2006;  3 1541-1555