title: Stability of yellow fever vaccine.
abstract: Yellow fever, an acute mosquito-borne viral haemorrhagic fever, is preventable by use of the live, attenuated 17D vaccine. The vaccine is used principally in tropical climates and is subject to potentially adverse conditions. Lyophilized vaccine without stabilizers deteriorates rapidly when exposed to temperatures above -20 degrees C. In 1987, the WHO recommended that each lot of vaccine meet the following stability test: maintenance of potency (> 1,000 mouse i.c.LD50/human dose) with mean loss of titre < 1.0 log10 after being held at 37 degrees C for 14 days. In 1987, only 5 out of 12 yellow fever vaccines produced worldwide met the stability standards. To improve stability of the vaccine, a number of additives have been systematically investigated. A successful formulation, now used by a number of manufacturers, employs sugars, amino acids, and divalent cations [lactose (4%), sorbitol (2%), histidine (0.01 M), alanine (0.01 M), in phosphate buffered saline with Ca2+ and Mg2+]. As opposed to vaccine produced without stabilizers, which loses 1.5-2.5 log10/dose, stabilized vaccines lose only 0.3-0.5 log10 after being held at 37 degrees C for 14 days. The vaccine is stable after storage for > or = two years at 4 degrees C and 22 degrees C, and has a stability profile as good or better than many other live and inactivated vaccines currently used in the EPI, including measles, pertussis, oral and inactivated poliomyelitis vaccines. WHO is taking steps to enssure that all 11 current YF vaccine manufacturers produce vaccines that meet accepted stability standards. The principal rationale for increasing 17D vaccine stability beyond that achieved with the present stabilizers would be the improvement in stability of other EPI vaccines, to the point where yellow fever vaccine was the most sensitive vaccine among those deployed. The acceptable characteristics of current stabilized 17D vaccines and the high cost of changing and validating new vaccine formulations precludes a major investment at this time. Despite its stability when freeze dried, yellow fever 17D vaccine is quite unstable after reconstitution and must be discarded after one hour. Improvement in vaccine stability after reconstitution would thus reduce cost, stretch supplies of vaccine, and ensure against vaccine failures due to use of degraded vaccine. This is an area for future research.
authors.affiliation: Research & Medical Affairs, OraVax Inc., Cambridge MA, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Monath
mesh_terms: D000818:Animals; D004355:Drug Stability; D004356:Drug Storage; D005544:Forecasting; D005612:Freeze Drying; D006801:Humans; D051379:Mice; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000276:immunology / Q000592:standards; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology / Q000592:standards; D014944:World Health Organization; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D011310:Preservatives, Pharmaceutical; D014613:Vaccines, Attenuated; D014765:Viral Vaccines