A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children

Science Translational Medicine

Volumn 7, Issue 312, 2015, Pages

  Karron, Ruth A ^a   Luongo, Cindy ^b   Thumar, Bhagvanji ^a   Loehr, Karen M ^a   Englund, Janet A ^c   Collins, Peter L ^b   Buchholz, Ursula J ^b  

^a JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NEUTRALIZING ANTIBODY; PLACEBO; RESPIRATORY SYNCYTIAL VIRUS VACCINE; LIVE VACCINE; M2-2 PROTEIN, RESPIRATORY SYNCYTIAL VIRUS; VIRUS ANTIBODY; VIRUS PROTEIN;

ADULT; ANTIBODY BLOOD LEVEL; ANTIBODY RESPONSE; ANTIBODY TITER; ARTICLE; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; COUGHING; DOUBLE BLIND PROCEDURE; DRUG SAFETY; FEMALE; FEVER; GENE DELETION; GENE EXPRESSION; GENETIC STABILITY; HOARSENESS; HUMAN; INFANT; INFECTION PREVENTION; MALE; MUCOCUTANEOUS LYMPH NODE SYNDROME; NONHUMAN; PHARYNGITIS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY SYNCYTIAL VIRUS INFECTION; RHINORRHEA; VIRUS INFECTIVITY; VIRUS REPLICATION; VIRUS SHEDDING; ANTIBODY PRODUCTION; GENE EXPRESSION REGULATION; GENETICS; HUMAN RESPIRATORY SYNCYTIAL VIRUS; IMMUNOLOGY; PRESCHOOL CHILD;

ADULT; ANTIBODIES, VIRAL; ANTIBODY FORMATION; CHILD, PRESCHOOL; GENE DELETION; GENE EXPRESSION REGULATION, VIRAL; HUMANS; INFANT; RESPIRATORY SYNCYTIAL VIRUS VACCINES; RESPIRATORY SYNCYTIAL VIRUSES; VACCINES, ATTENUATED; VIRAL PROTEINS;

EID: 84947247579     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aac8463     Document Type: Article

References (27)

1. C. B. Hall, G. A. Weinberg, M. K. Iwane, A. K. Blumkin, K. M. Edwards, M. A. Staat, P. Auinger, M. R. Griffin, K. A. Poehling, D. Erdman, C. G. Grijalva, Y. Zhu, P. Szilagyi, The burden of respiratory syncytial virus infection in young children. N. Engl. J. Med. 360, 588-598 (2009).
2. H. Nair, D. J. Nokes, B. D. Gessner, M. Dherani, S. A. Madhi, R. J. Singleton, K. L O'Brien, A. Roca, P. F. Wright, N. Bruce, A. Chandran, E. Theodoratou, A. Sutanto, E. R. Sedyaningsih, M. Ngama, P. K. Munywoki, C Kartasasmita, E. A. F. Simões, I. Rudan, M. W. Weber, H. Campbell, Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 375, 1545-1555 (2010).
3. D. K. Shay, R. C Holman, R. D. Newman, L. L Liu, J. W. Stout, L. J. Anderson, Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 282, 1440-1446 (1999).
4. O. S. Levine, M. D. Knoll, A. Jones, D. G. Walker, N. Risko, Z. Gilani, Global status of Haemophilus influenzae type b and pneumococcal conjugate vaccines: Evidence, policies, and introductions. Curr. Opin. Infect. Dis. 23, 236-241 (2010).
5. P. L. Collins, J. A. Melero, Progress in understanding and controlling respiratory syncytial virus: Still crazy after all these years. Virus Res. 162, 80-99 (2011).
6. B. S. Graham, L. J. Anderson, Challenges and opportunities for respiratory syncytial virus vaccines. Curr. Top. Microbiol. Immunol. 372, 391-404 (2013).
7. P. F. Wright, R. A. Karron, R. B. Belshe, J. Thompson, J. E. Crowe Jr., T. G. Boyce, L L. Halburnt, G. W. Reed, S. S. Whitehead, E. L. Anderson, A. E. Wittek, R. Casey, M. Eichelberger, B. Thumar, V. B. Randolph, S. A. Udem, R. M. Chanock, B. R. Murphy, Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy. J. Infect. Dis. 182, 1331-1342 (2000).
8. R. A. Karron, P. F. Wright, R. B. Belshe, B. Thumar, R. Casey, F. Newman, F. P. Polack, V. B. Randolph, A. Deatly, J. Hackell, W. Gruber, B. R. Murphy, P. L Collins, Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants. J. Infect. Dis. 191, 1093-1104 (2005).
9. P. F. Wright, R. A. Karron, S. A. Madhi, J. J. Treanor, J. C. King, A. O'Shea, M. R. Ikizler, Y. Zhu, P. L Collins, C Cutland, V. B. Randolph, A. M. Deatly, J. G. Hackell, W. C. Gruber, B. R. Murphy, The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans. J. Infect. Dis. 193, 573-581 (2006).
10. P. F. Wright, R. A. Karron, R. B. Belshe, J. R. Shi, V. B. Randolph, P. L Collins, A. F. O'Shea, W C. Gruber, B. R. Murphy, The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines. Vaccine 25, 7372-7378 (2007).
11. E. Malkin, R. Yogev, N. Abughali, J. Sliman, C K. Wang, F. Zuo, C.-F. Yang, M. Eickhoff, M. T. Esser, R. S. Tang, F. Dubovsky, Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age. PLOS One 8, e77104 (2013).
12. H. W. Kim, J. G. Canchola, C. D. Brandt, G. Pyles, R. M. Chanock, K. Jensen, R. H. Parrott, Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am. J. Epidemiol. 89, 422-434 (1969).
13. B. R. Murphy, A. V. Sotnikov, L. A. Lawrence, S. M. Banks, G. A. Prince, Enhanced pulmonary histopathology is observed in cotton rats immunized with formalin-inactivated respiratory syncytial virus (RSV) or purified F glycoprotein and challenged with RSV 3-6 months after immunization. Vaccine 8, 497-502 (1990).
14. M. Connors, P. L. Collins, C.-Y. Firestone, A. V. Sotnikov, A. Waitze, A. R. Davis, P. P. Hung, R. M. Chanock, B. R. Murphy, Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia - RSV recombinants or RSV. Vaccine 10, 475-484 (1992).
15. R. A. Karron, P. F. Wright, J. E. Crowe Jr., M. L Clements Mann, J. Thompson, M. Makhene, R. Casey, B. R. Murphy, Evaluation of two live, cold-passaged, temperature-sensitive respiratory syncytial virus vaccines in chimpanzees and in human adults, infants and children. J. Infect. Dis. 176, 1428-1436 (1997).
16. P. L. Collins, M. G. Hill, E. Camargo, H. Grosfeld, R. M. Chanock, B. R. Murphy, Production of infectious human respiratory syncytial virus from cloned cDNA confirms an essential role for the transcription elongation factor from the 5' proximal open reading frame of the M2 mRNA in gene expression and provides a capability for vaccine development. Proc. Natl. Acad. Sci. U.S.A. 92, 11563-11567 (1995).
17. A. Bermingham, P. L. Collins, The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription. Proc. Natl. Acad. Sci. U.S.A. 96, 11259-11264 (1999).
18. M. N. Teng, S. S. Whitehead, A. Bermingham, M. St. Claire, W. R. Elkins, B. R. Murphy, P. L. Collins, Recombinant respiratory syncytial virus that does not express the NS1 or M2-2 protein is highly attenuated and immunogenic in chimpanzees. J. Virol. 74, 9317-9321 (2000).
19. H. Jin, H. Zhou, X. Cheng, R. Tang, M. Munoz, N. Nguyen, Recombinant respiratory syncytial viruses with deletions in the NS1, NS2, SH, and M2-2 genes are attenuated in vitro and in vivo. Virology 273, 210-218 (2000).
20. J. A. Englund, R. A. Karron, C. K. Cunningham, P. LaRussa, A. Melvin, R. Yogev, E. Handelsman, G. K. Siberry, B. Thumar, E. Schappell, C. V. Bull, H. Y. Chu, A. Schaap-Nutt, U. Buchholz, P. L. Collins, A. C. Schmidt; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1096 Study Group, Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children. Vaccine 31, 5706-5712 (2013).
21. R. A. Karron, U. J. Buchholz, P. L. Collins, Live-attenuated respiratory syncytial virus vaccines. Curr. Top. Microbiol. Immunol. 372, 259-284 (2013).
22. T. Vesikari, A. Karvonen, T. Korhonen, K. Edelman, R. Vainionpää, A. Salmi, M. K. Saville, I. Cho, A. Razmpour, R. Rappaport, R. O'Neill, A. Georgiu, W. Gruber, P. M. Mendelman, B. Forrest; CAIV-T Transmission Study Group, A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine. Pediatr. Infect. Dis. J. 25, 590-595 (2006).
23. W. P. Glezen, L. H. Taber, A. L. Frank, J. A. Kasel, Risk of primary infection and reinfection with respiratory syncytial virus. Am. J. Dis. Child. 140, 543-546 (1986).
24. G. R. Siber, D. Leombruno, J. Leszczynski, J. McIver, D. Bodkin, R. Gonin, C. M. Thompson, E. E. Walsh, P. A. Piedra, V. G. Hemming, G. A. Prince, Comparison of antibody concentrations and protective activity of respiratory syncytial virus immune globulin and conventional immune globulin. J. Infect. Dis. 169, 1368-1373 (1994).
25. J. R. Groothuis, E. A. Simoes, M. J. Levin, C. B. Hall, C. E. Long, W. J. Rodriguez, J. Arrobio, H. C. Meissner, D. R. Fulton, R. C. Welliver, D. A. Tristram, G. R. Siber, G. A. Prince, M. Van Raden, V. G. Hemming; Respiratory Syncytial Virus Immune Globulin Study Group, Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. N. Engl. J. Med. 329, 1524-1530 (1993).
26. H. V. Coates, D. W. Alling, R. M. Chanock, An antigenic analysis of respiratory syncytial virus isolates by a plaque reduction neutralization test. Am. J. Epidemiol. 83, 299-313 (1966).
27. G. Smith, R. Raghunandan, Y. Wu, Y. Liu, M. Massare, M. Nathan, B. Zhou, H. Lu, S. Boddapati, J. Li, D. Flyer, G. Glenn, Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats. PLOS One 7, e50852 (2012).