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Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator.
Clin Vaccine Immunol. 2017 12; 24(12)CV

Abstract

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 × 108 CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 × 109 CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 × 108-CFU standard dose (n = 50) or a ≥2 × 109-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ∼2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.).

Authors+Show Affiliations

Centre pour le Développement des Vaccins, Bamako, Mali. Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Centre pour le Développement des Vaccins, Bamako, Mali. Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Centre pour le Développement des Vaccins, Bamako, Mali.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA. Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.Centre pour le Développement des Vaccins, Bamako, Mali.Centre pour le Développement des Vaccins, Bamako, Mali.Centre pour le Développement des Vaccins, Bamako, Mali.Centre pour le Développement des Vaccins, Bamako, Mali.Centre pour le Développement des Vaccins, Bamako, Mali.Centre pour le Développement des Vaccins, Bamako, Mali.Centre pour le Développement des Vaccins, Bamako, Mali.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA. Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.PaxVax, Inc., Redwood City, California, USA.PaxVax, Inc., Redwood City, California, USA.PaxVax, Inc., Redwood City, California, USA.PaxVax, Inc., Redwood City, California, USA.PaxVax, Inc., Redwood City, California, USA.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA mlevine@som.umaryland.edu.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29021299

Citation

Sow, Samba O., et al. "Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, With Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator." Clinical and Vaccine Immunology : CVI, vol. 24, no. 12, 2017.
Sow SO, Tapia MD, Chen WH, et al. Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator. Clin Vaccine Immunol. 2017;24(12).
Sow, S. O., Tapia, M. D., Chen, W. H., Haidara, F. C., Kotloff, K. L., Pasetti, M. F., Blackwelder, W. C., Traoré, A., Tamboura, B., Doumbia, M., Diallo, F., Coulibaly, F., Onwuchekwa, U., Kodio, M., Tennant, S. M., Reymann, M., Lam, D. F., Gurwith, M., Lock, M., ... Levine, M. M. (2017). Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator. Clinical and Vaccine Immunology : CVI, 24(12). https://doi.org/10.1128/CVI.00265-17
Sow SO, et al. Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, With Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator. Clin Vaccine Immunol. 2017;24(12) PubMed PMID: 29021299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator. AU - Sow,Samba O, AU - Tapia,Milagritos D, AU - Chen,Wilbur H, AU - Haidara,Fadima C, AU - Kotloff,Karen L, AU - Pasetti,Marcela F, AU - Blackwelder,William C, AU - Traoré,Awa, AU - Tamboura,Boubou, AU - Doumbia,Moussa, AU - Diallo,Fatoumata, AU - Coulibaly,Flanon, AU - Onwuchekwa,Uma, AU - Kodio,Mamoudou, AU - Tennant,Sharon M, AU - Reymann,Mardi, AU - Lam,Diana F, AU - Gurwith,Marc, AU - Lock,Michael, AU - Yonker,Thomas, AU - Smith,Jonathan, AU - Simon,Jakub K, AU - Levine,Myron M, Y1 - 2017/12/05/ PY - 2017/09/07/received PY - 2017/10/02/accepted PY - 2017/10/13/pubmed PY - 2019/7/23/medline PY - 2017/10/13/entrez KW - Mali KW - cholera vaccine KW - immunogenicity KW - live oral vaccine KW - reactive vaccination KW - single-dose vaccine JF - Clinical and vaccine immunology : CVI JO - Clin. Vaccine Immunol. VL - 24 IS - 12 N2 - Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 × 108 CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 × 109 CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 × 108-CFU standard dose (n = 50) or a ≥2 × 109-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ∼2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.). SN - 1556-679X UR - https://www.unboundmedicine.com/medline/citation/29021299/Randomized_Placebo_Controlled_Double_Blind_Phase_2_Trial_Comparing_the_Reactogenicity_and_Immunogenicity_of_a_Single_Standard_Dose_to_Those_of_a_High_Dose_of_CVD_103_HgR_Live_Attenuated_Oral_Cholera_Vaccine_with_Shanchol_Inactivated_Oral_Vaccine_as_an_Open_Label_Immunologic_Comparator_ L2 - http://cvi.asm.org/cgi/pmidlookup?view=long&pmid=29021299 DB - PRIME DP - Unbound Medicine ER -