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Molecular characterization of the 17D-204 yellow fever vaccine.
Vaccine. 2015 Oct 05; 33(41):5432-5436.V

Abstract

INTRODUCTION

The worldwide use of yellow fever (YF) live attenuated vaccines came recently under close scrutiny as rare but serious adverse events have been reported. The population identified at major risk for these safety issues were extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the French National Agency for AIDS research is an ongoing interventional study to evaluate the safety of the vaccine and the specific immune responses in HIV-infected patients following 17D-204 vaccination. As a preliminary study, we characterized the molecular diversity from E gene of the single 17D-204 vaccine batch used in this clinical study.

MATERIALS AND METHODS

Eight vials of lyophilized 17D-204 vaccine (Stamaril, Sanofi-Pasteur, Lyon, France) of the E5499 batch were reconstituted for viral quantification, cloning and sequencing of C/prM/E region.

RESULTS

The average rate of virions per vial was 8.68 ± 0.07 log₁₀ genome equivalents with a low coefficient of variation (0.81%). 246 sequences of the C/prM/E region (29-33 per vials) were generated and analyzed for the eight vials, 25 (10%) being defective and excluded from analyses. 95% of sequences had at least one nucleotide mutation. The mutations were observed on 662 variant sites distributed through all over the 1995 nucleotides sequence and were mainly non-synonymous (66%). Genome variability between vaccine vials was highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%. Average p-distances observed for each vial were also homogeneous, ranging from 0.15% to 0.31%.

CONCLUSION

This study showed a homogenous YF virus RNA quantity in vaccine vials within a single lot and a low clonal diversity inter and intra vaccine vials. These results are consistent with a recent study showing that the main mechanism of attenuation resulted in the loss of diversity in the YF virus quasi-species.

Authors+Show Affiliations

Univ Paris Diderot, Pres Sorbone Paris Cité, Microbiology Laboratory, Hôpital Universitaire Saint-Louis, 75475 Paris 10, France. Electronic address: maud.salmona@aphp.fr.Univ Paris Diderot, Pres Sorbone Paris Cité, Infectious Diseases Department, Hôpital Universitaire Saint-Louis, 75475 Paris 10, France.Univ Paris Diderot, Pres Sorbone Paris Cité, Microbiology Laboratory, Hôpital Universitaire Saint-Louis, 75475 Paris 10, France.Agence Nationale de la Sécurité du Médicament, ANSM site de Lyon 321, 69007 Lyon, France.Agence Nationale de la Sécurité du Médicament, ANSM site de Lyon 321, 69007 Lyon, France.Univ Paris Diderot, Pres Sorbone Paris Cité, Infectious Diseases Department, Hôpital Universitaire Saint-Louis, 75475 Paris 10, France.Univ Paris Diderot, Pres Sorbone Paris Cité, Microbiology Laboratory, Hôpital Universitaire Saint-Louis, 75475 Paris 10, France.Service d'Immuno-Virologie, Institute of Emerging Diseases and Innovative Therapies, Commissariat à l'Energie Atomique, 92260 Fontenay aux Roses, France.Univ Paris Diderot, Pres Sorbone Paris Cité, Microbiology Laboratory, Hôpital Universitaire Saint-Louis, 75475 Paris 10, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26314624

Citation

Salmona, Maud, et al. "Molecular Characterization of the 17D-204 Yellow Fever Vaccine." Vaccine, vol. 33, no. 41, 2015, pp. 5432-5436.
Salmona M, Gazaignes S, Mercier-Delarue S, et al. Molecular characterization of the 17D-204 yellow fever vaccine. Vaccine. 2015;33(41):5432-5436.
Salmona, M., Gazaignes, S., Mercier-Delarue, S., Garnier, F., Korimbocus, J., Colin de Verdière, N., LeGoff, J., Roques, P., & Simon, F. (2015). Molecular characterization of the 17D-204 yellow fever vaccine. Vaccine, 33(41), 5432-5436. https://doi.org/10.1016/j.vaccine.2015.08.055
Salmona M, et al. Molecular Characterization of the 17D-204 Yellow Fever Vaccine. Vaccine. 2015 Oct 5;33(41):5432-5436. PubMed PMID: 26314624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular characterization of the 17D-204 yellow fever vaccine. AU - Salmona,Maud, AU - Gazaignes,Sandrine, AU - Mercier-Delarue,Severine, AU - Garnier,Fabienne, AU - Korimbocus,Jehanara, AU - Colin de Verdière,Nathalie, AU - LeGoff,Jerome, AU - Roques,Pierre, AU - Simon,François, Y1 - 2015/08/24/ PY - 2015/05/23/received PY - 2015/08/02/revised PY - 2015/08/05/accepted PY - 2015/8/29/entrez PY - 2015/9/1/pubmed PY - 2016/6/18/medline KW - Genetic diversity KW - Vaccine KW - Yellow fever SP - 5432 EP - 5436 JF - Vaccine JO - Vaccine VL - 33 IS - 41 N2 - INTRODUCTION: The worldwide use of yellow fever (YF) live attenuated vaccines came recently under close scrutiny as rare but serious adverse events have been reported. The population identified at major risk for these safety issues were extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the French National Agency for AIDS research is an ongoing interventional study to evaluate the safety of the vaccine and the specific immune responses in HIV-infected patients following 17D-204 vaccination. As a preliminary study, we characterized the molecular diversity from E gene of the single 17D-204 vaccine batch used in this clinical study. MATERIALS AND METHODS: Eight vials of lyophilized 17D-204 vaccine (Stamaril, Sanofi-Pasteur, Lyon, France) of the E5499 batch were reconstituted for viral quantification, cloning and sequencing of C/prM/E region. RESULTS: The average rate of virions per vial was 8.68 ± 0.07 log₁₀ genome equivalents with a low coefficient of variation (0.81%). 246 sequences of the C/prM/E region (29-33 per vials) were generated and analyzed for the eight vials, 25 (10%) being defective and excluded from analyses. 95% of sequences had at least one nucleotide mutation. The mutations were observed on 662 variant sites distributed through all over the 1995 nucleotides sequence and were mainly non-synonymous (66%). Genome variability between vaccine vials was highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%. Average p-distances observed for each vial were also homogeneous, ranging from 0.15% to 0.31%. CONCLUSION: This study showed a homogenous YF virus RNA quantity in vaccine vials within a single lot and a low clonal diversity inter and intra vaccine vials. These results are consistent with a recent study showing that the main mechanism of attenuation resulted in the loss of diversity in the YF virus quasi-species. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/26314624/Molecular_characterization_of_the_17D_204_yellow_fever_vaccine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(15)01183-4 DB - PRIME DP - Unbound Medicine ER -