A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men

Stuart P. Adler, Anne Marie Manganello, Ronzo Lee, Michael A. McVoy, Daniel E. Nixon, Stanley Plotkin, Edward Mocarski, Josephine H. Cox, Patricia E. Fast, Pavlo A. Nesterenko, Susan Murray, Ann Hill, George Kemble

Research output: Contribution to journalArticle

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Abstract

Background. Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients. Methods. The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted. Results. There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+ T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+ T-cell responses to IE1; 3 responded to 1-2 additional antigens. Conclusions. The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate. Clinical Trials Registration. NCT01195571.

Original languageEnglish (US)
Pages (from-to)1341-1348
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number9
DOIs
StatePublished - Nov 1 2016

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Cytomegalovirus Vaccines
Cytomegalovirus
Vaccines
T-Lymphocytes
Cytomegalovirus Infections
Saliva
Immunization

Keywords

  • cytomegalovirus
  • pregnancy
  • transplantation
  • vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Adler, S. P., Manganello, A. M., Lee, R., McVoy, M. A., Nixon, D. E., Plotkin, S., ... Kemble, G. (2016). A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men. Journal of Infectious Diseases, 214(9), 1341-1348. https://doi.org/10.1093/infdis/jiw365

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men. / Adler, Stuart P.; Manganello, Anne Marie; Lee, Ronzo; McVoy, Michael A.; Nixon, Daniel E.; Plotkin, Stanley; Mocarski, Edward; Cox, Josephine H.; Fast, Patricia E.; Nesterenko, Pavlo A.; Murray, Susan; Hill, Ann; Kemble, George.

In: Journal of Infectious Diseases, Vol. 214, No. 9, 01.11.2016, p. 1341-1348.

Research output: Contribution to journalArticle

Adler, SP, Manganello, AM, Lee, R, McVoy, MA, Nixon, DE, Plotkin, S, Mocarski, E, Cox, JH, Fast, PE, Nesterenko, PA, Murray, S, Hill, A & Kemble, G 2016, 'A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men', Journal of Infectious Diseases, vol. 214, no. 9, pp. 1341-1348. https://doi.org/10.1093/infdis/jiw365
Adler, Stuart P. ; Manganello, Anne Marie ; Lee, Ronzo ; McVoy, Michael A. ; Nixon, Daniel E. ; Plotkin, Stanley ; Mocarski, Edward ; Cox, Josephine H. ; Fast, Patricia E. ; Nesterenko, Pavlo A. ; Murray, Susan ; Hill, Ann ; Kemble, George. / A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 9. pp. 1341-1348.
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abstract = "Background. Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients. Methods. The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted. Results. There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+ T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+ T-cell responses to IE1; 3 responded to 1-2 additional antigens. Conclusions. The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate. Clinical Trials Registration. NCT01195571.",
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AU - Lee, Ronzo

AU - McVoy, Michael A.

AU - Nixon, Daniel E.

AU - Plotkin, Stanley

AU - Mocarski, Edward

AU - Cox, Josephine H.

AU - Fast, Patricia E.

AU - Nesterenko, Pavlo A.

AU - Murray, Susan

AU - Hill, Ann

AU - Kemble, George

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N2 - Background. Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients. Methods. The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted. Results. There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+ T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+ T-cell responses to IE1; 3 responded to 1-2 additional antigens. Conclusions. The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate. Clinical Trials Registration. NCT01195571.

AB - Background. Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients. Methods. The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted. Results. There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+ T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+ T-cell responses to IE1; 3 responded to 1-2 additional antigens. Conclusions. The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate. Clinical Trials Registration. NCT01195571.

KW - cytomegalovirus

KW - pregnancy

KW - transplantation

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