Yellow fever vaccine-associated adverse events following extensive immunization in Argentina

Serious adverse events associated with yellow fever vaccine

“…In a dose-response study viremias by virus isolation, qRT-PCR, and clinical reactogenicity were statistically similar across the different study arms, with deescalating doses from 27,476 IU (approximately 52,000 PFU, the usual dose) to 31 IU (approximately 60 PFU) 32 Mass vaccination campaigns include errors administering vaccines in doses from 10 times to 25 times the recommended dose (n D 163), but there were no serious adverse events. 13,33,34 Moreover, in BioManguinhos/Fiocruz, the release titers are verified for all lots and have been around 70,000 PFU/human dose and within narrow limits of variation across different lots along the last decades, showing a very consistent and homogeneous production. So, this hypothesis seems untenable.…”

“…12 In a study of adverse events during a campaign in Argentina, 13 there was one YEL-AVD confirmed case per 1,943,000 doses administered (0.05/100,000 doses). Including 12 probable cases, the rate increased to 0.6/100,000 doses, 7/12 were in people >50 years old (but risk per age group is not provided), and 9/12 were male.…”

The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon

“…As no replication defect was seen for the K6R mutant virus in mock-treated Vero cells, it appears that K6 may only be important for IFN antagonism. YFV-17D causes neurotropic and viscerotropic disease in immune-compromised individuals (Barrett et al, 2007; Biscayart et al, 2014; Breugelmans et al, 2013; Klein et al, 2010; Lindsey et al, 2008; Monath et al, 2005). Decreasing the ability of YFV-17D to antagonize IFN-I signaling may limit the replication of this vaccine in immunocompromised individuals thereby decreasing the incidence of vaccine-associated adverse events.…”

“…Even in the case of YFV, for which there is a highly efficacious vaccine, there are 200,000 reported cases annually with at least 30,000 deaths (Barrett and Monath, 2007). Despite the success of the live-attenuated YFV-17D vaccine, occurrences of vaccine-associated viscerotropic and neurotropic disease have brought its safety into question (Barrett et al, 2007; Biscayart et al, 2014; Breugelmans et al, 2013; Monath et al, 2005). …”

Questions regarding the safety and duration of immunity following live yellow fever vaccination

“…However, this number may be heavily skewed since 432 million doses (94%) were distributed in endemic countries. When the analysis is specifically limited to endemic countries ([64,65,75,76] and the endemic subpopulation in [63]) there are 0.38 cases of YEL-AND per million doses (165 cases from approximately 432 million vaccinations). After correcting for the number of administered military doses in [68], analysis from this study and the three other references cited by the CDC [11] in non-endemic regions ([62,68,77], and the non-endemic subpopulation in [63]), together totaled 43 cases of YEL-AND among approximately 22.5 million vaccinations (1.9 YEL-AND per million doses).…”