Phase 2 Evaluation of Parainfluenza Type 3 Cold Passage Mutant 45 Live Attenuated Vaccine in Healthy Children 6–18 Months Old

Belshe, Robert B.; Newman, Frances K.; Tsai, Theodore F.; Karron, Ruth A.; Reisinger, Keith S.; Roberton, Don; Marshall, Helen; Schwartz, Richard; King, James C.; Henderson, Frederick W.; Rodríguez, William J.; Severs, Joseph; Wright, Peter F.; Keyserling, Harry L.; Weinberg, Geoffrey A.; Bromberg, Kenneth; Loh, Richard; Sly, Peter D.; McIntyre, Peter; Ziegler, John B.; Hackell, Jill G.; Deatly, Anne M.; Georgiu, Alice; Paschalis, Maribel; Wu, Shin Lu; Tatem, Joanne M.; Murphy, Brian R.; Anderson, Edwin L.

doi:10.1086/381184

Cited by 53 publications

(35 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experimental inactivated (RSV and HPIV3) and subunit (RSV) vaccines have been linked to vaccine-induced enhanced disease in young children (inactivated RSV) and experimental animals (subunit RSV and inactivated HPIV3) (2)(3)(4). In contrast, disease enhancement is not observed with live attenuated RSV strains or vectors expressing RSV antigens (5)(6)(7), indicating that suitably attenuated candidates are safe for immunization of infants and young children.…”

mentioning

confidence: 99%

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

Liang

Surman

Amaro-Carambot

et al. 2015

J Virol

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. H uman respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are enveloped, nonsegmented, negative-stranded RNA viruses of the family Paramyxoviridae. They are, respectively, the first and second leading viral causes of severe acute lower respiratory tract infections in infants and children worldwide. RSV alone is responsible for an estimated 34 million annual pediatric cases of lower respiratory tract illness worldwide, with Ͼ3.5 million hospitalizations and 66,000 to 199,000 pediatric deaths, which occur predominantly in the developing world (1). Licensed vaccines or effective antiviral drugs are not available for either RSV or HPIV3. Experimental inactivated (RSV and HPIV3) and subunit (RSV) vaccines have been linked to vaccine-induced enhanced disease in young children (inactivated RSV) and experimental animals (subunit RSV and inactivated HPIV3) (2-4). In contrast, disease enhancement is not observed with live attenuated RSV strains or vectors expressing RSV antigens (5-7), indicating that suitably attenuated candidates are safe for immunization of infants and young children.A chimeric recombinant bovine-human PIV3 (rB/HPIV3) ( Fig. 1) has been under development as a replication-competent intranasal pediatric vaccine vector. The PIV3 genome is a negative-sense RNA of 15.5 kb that contains six genes in the order 3=-N (nucleoprotein)-P (phosphoprotein)-M (matrix protein)-F (fusion glycoprotein)...

show abstract

mentioning

confidence: 99%

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

Liang

Surman

Amaro-Carambot

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…It is reported to have a 94% infectivity rate and lacks transmissibility [104][105][106] . A larger phase II study with a population size of 380 children aged 6-18 months, consisting of 226 seronegative children demonstrated that it generated adequate antibody response in 84% of seronegative recipients with no significant difference in adverse events when compared to placebo 107 .…”

Section: Rsv Vaccine Developmentmentioning

confidence: 99%

Vaccines in the Prevention of Viral Pneumonia

Fraser

Jha

Openshaw

2017

Clinics in Chest Medicine

View full text Add to dashboard Cite

“…Belshe et al [38] evaluated the protective properties of a live attenuated PIV3-cp45 vaccine candidate in 380 children in a Phase II trial. The 226 seronegative children were divided: 114 were vaccinated and 112 received placebo.…”

Section: Piv1 and Piv3 Xenogeneic Recombinant Rsv Vaccinesmentioning

confidence: 99%

Past, present and future of RSV and PIV vaccines and anti-RSV antibodies for the protection of humans against RSV

Becker

2007

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

Expert Opin. Ther. Patents (2007) 17(8):941-953 Expert Opin. Ther. Patents Downloaded from informahealthcare.com by McMaster University on 11/25/14 For personal use only. Past, present and future of RSV and PIV vaccines and anti-RSV antibodies for the protection of humans against RSV 942 Expert Opin. Ther. Patents (2007) 17(8) Expert Opin. Ther. Patents Downloaded from informahealthcare.com by McMaster University on 11/25/14 For personal use only.

show abstract

Phase 2 Evaluation of Parainfluenza Type 3 Cold Passage Mutant 45 Live Attenuated Vaccine in Healthy Children 6–18 Months Old

Cited by 53 publications

References 17 publications

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

Vaccines in the Prevention of Viral Pneumonia

Past, present and future of RSV and PIV vaccines and anti-RSV antibodies for the protection of humans against RSV

Contact Info

Product

Resources

About