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An inactivated cell-culture vaccine against yellow fever.
N Engl J Med. 2011 Apr 07; 364(14):1326-33.NEJM

Abstract

BACKGROUND

Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed.

METHODS

In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42.

RESULTS

The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine.

CONCLUSIONS

A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).

Authors+Show Affiliations

Xcellerex, Marlborough, MA, USA. tmonath@kpcb.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21470010

Citation

Monath, Thomas P., et al. "An Inactivated Cell-culture Vaccine Against Yellow Fever." The New England Journal of Medicine, vol. 364, no. 14, 2011, pp. 1326-33.
Monath TP, Fowler E, Johnson CT, et al. An inactivated cell-culture vaccine against yellow fever. N Engl J Med. 2011;364(14):1326-33.
Monath, T. P., Fowler, E., Johnson, C. T., Balser, J., Morin, M. J., Sisti, M., & Trent, D. W. (2011). An inactivated cell-culture vaccine against yellow fever. The New England Journal of Medicine, 364(14), 1326-33. https://doi.org/10.1056/NEJMoa1009303
Monath TP, et al. An Inactivated Cell-culture Vaccine Against Yellow Fever. N Engl J Med. 2011 Apr 7;364(14):1326-33. PubMed PMID: 21470010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An inactivated cell-culture vaccine against yellow fever. AU - Monath,Thomas P, AU - Fowler,Elizabeth, AU - Johnson,Casey T, AU - Balser,John, AU - Morin,Merribeth J, AU - Sisti,Maggie, AU - Trent,Dennis W, PY - 2011/4/8/entrez PY - 2011/4/8/pubmed PY - 2011/4/13/medline SP - 1326 EP - 33 JF - The New England journal of medicine JO - N Engl J Med VL - 364 IS - 14 N2 - BACKGROUND: Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. METHODS: In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. RESULTS: The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. CONCLUSIONS: A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/21470010/An_inactivated_cell_culture_vaccine_against_yellow_fever_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa1009303?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -