Major Areas of Research
- Studies in molecular biology, immunobiology, and pathogenesis of the human respiratory pathogens respiratory syncytial virus (RSV), human parainfluenza virus (HPIV) serotypes 1, 2, and 3, and human metapneumovirus (HMPV)
- Studies involve infection in vitro of epithelial cells, macrophages, and other cell types and in vivo infection of experimental animals to elucidate the viral replicative cycle, interactions between viral and host components, the host response to infection, and mechanisms of pathogenesis. Studies include mini-replicons, complete recombinant virus, and engineered viral variants with gene knock-outs or mutated proteins.
- Development of novel attenuating mutations that are introduced by reverse genetics into RSV, HPIV1, 2, and 3, and HMPV to produce live, attenuated “designer” vaccine candidates
- Candidates are evaluated preclinically in monolayer cell cultures, in vitro models of airway epithelium, rodents, and nonhuman primates.
- Evaluation of candidate live vaccines in clinical studies with clinical collaborators, as well as wild type viruses in adult volunteers
- Studies with wild type and “designer” mutants of pneumonia virus of mice (PVM), a relative of RSV, in mice to characterize viral infection and host responses to an RSV-like virus in a convenient permissive host
- Development of vaccine vectors based on HPIV and avian paramyxoviruses (APMVs) such as Newcastle disease virus (NDV) for use against highly pathogenic emerging viruses exemplified by SARS coronavirus, avian influenza, and Ebola viruses
Dr. Collins’ laboratory works with paramyxoviruses, which are enveloped, cytoplasmic viruses with single-stranded negative-sense RNA genomes of 13-19 kb. Paramyxoviruses include a number of well-known, important pathogens of humans (e.g., mumps and measles viruses) and animals (e.g., rinderpest and NDV), and also include emerging pathogens (e.g., Nipah and Hendra viruses). Dr. Collins played a pioneering role in sequencing and characterizing the genomes and encoded gene products of several paramyxoviruses, in particular human RSV. Later, he played an important role in developing reverse genetics systems for this type of virus, whereby complete infectious virus can be recovered from transfected cDNAs. This provides the basis for introducing predetermined changes into infectious virus for basic research and for vaccine development.
RSV is a leading worldwide agent of respiratory tract disease, especially in young infants. The laboratory also studies several other major pediatric respiratory pathogens, namely HPIV1, 2, and 3 and HMPV. Other areas of interest include the APMVs, represented by NDV, and the murine relative of RSV called PVM. The laboratory is presently using reverse genetics to design live, attenuated vaccines for RSV, HPIV1, 2, and 3, and HMPV for intranasal administration to infants as a pediatric vaccine. In studies supported in part by collaboration with industry, lead candidates for RSV, HPIV1, 2, and 3, and HMPV are in Phase I, and in some cases Phase II, clinical trials. The laboratory also is using NDV and other APMVs as vaccine vectors to express protective antigens of emerging pathogens. The laboratory also investigates basic features of viral molecular biology, pathogenesis, and immunobiology that provide an intellectual foundation for the translational vaccine studies.
Dr. Collins received a Ph.D. in 1981 from the University of Connecticut. He conducted postdoctoral research at the University of North Carolina from 1981 to 1984. At that time, he joined the Laboratory of Infectious Diseases, where he received tenure in 1990. He serves on the editorial boards of the Journal of Virology, Virology, and Virus Research.
Sonja Barbagallo, Ursula Buchholz, Divya Gangaramani, Cyril Le Nouen, Bo Liang, M Lingemann, Xiang, Liu, Xueqiao Liu, Cindy Luongo, Thomas McCarty, Masfique Mehedi, Annie Moseman, Shirin Munir, Lijuan Yang
Luongo C, Winter CC, Collins PL, Buchholz UJ. Increased genetic and phenotypic stability of a promising live-attenuated respiratory syncytial virus vaccine candidate by reverse genetics. J Virol. 2012 Oct;86(19):10792-804.
Brock LG, Karron RA, Krempl CD, Collins PL, Buchholz UJ. Evaluation of pneumonia virus of mice as a possible human pathogen.J Virol. 2012 May;86(10):5829-43.
Schomacker H, Hebner RM, Boonyaratanakornkit J, Surman S, Amaro-Carambot E, Collins PL, Schmidt AC. The C proteins of human parainfluenza virus type 1 block IFN signaling by binding and retaining Stat1 in perinuclear aggregates at the late endosome.PLoS One. 2012;7(2):e28382.
Karron RA, Casey R, Thumar B, Surman S, Murphy BR, Collins PL, Schmidt AC. The cDNA-derived investigational human parainfluenza virus type 3 vaccine rcp45 is well tolerated, infectious, and immunogenic in infants and young children. Pediatr Infect Dis J. 2011 Oct;30(10):e186-91
Le Nouën C, Hillyer P, Winter CC, McCarty T, Rabin RL, Collins PL, Buchholz UJ. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus. PLoS Pathog. 2011 Jun;7(6):e1002105.
Subbiah M, Khattar SK, Collins PL, Samal SK. Mutations in the fusion protein cleavage site of avian paramyxovirus serotype 2 increase cleavability and syncy tium formation but do not increase viral virulence in chickens. J Virol. 2011 Jun;85(11):5394-405.
Murphy BR, Collins PL, Skiadopoulos MH, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Attenuated parainfluenza (PIV) vaccines. United States patent US 7,951,383. 31 May 2011.
Skiadopoulos MH, Murphy BR, Collins PL, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recovery of recombinant human parainfluenza virus type 2 (HPIV2) from CDNA and use of recombinant HPIV2 in immunogenic compositions and as vectors to elicit immune responses against PIV and other human pathogens. United States patent US 7,919,301. 5 Apr 2011.
Collins PL, Murphy BR, Whitehead SS, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Attenuated chimeric respiratory syncytial virus. United States patent US 7,846,455. 7 Dec 2010.
Buchholz U, Collins PL, Murphy BR, Whitehead SS, Krempl CD, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Production of attenuated, human-bovine chimeric respiratory syncytial virus vaccines. United States patent US 7,842,798. 30 Nov 2010.
Krempl CD, Collins PL, Murphy BR, Buchholz U, Whitehead SS, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes. United States patent US 7,744,902. 29 Jun 2010.
Murphy BR, Collins PL, Whitehead SS, Bukreyev AA, Juhasz K, Teng MN, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Production of attenuated respiratory syncytial virus vaccines from clones nucleotide sequences. United States patent US 7,709,007. 4 May 2010.