Abstract
The present study aims to determine whether 17DD-YF-specific humoral and cellular immunological memory is maintained 8-years after primary vaccination with subdoses (10,447IU;3,013IU;587IU;158IU;31IU). For this purpose, this follow-up study was carried out in a subset of volunteers (n = 98) originally enrolled in the dose-response study in 2009 and 46 non-vaccinated controls. Our results demonstrated that vaccinees, who had seroconverted following primary vaccination and had not been revaccinated, present similar neutralizing antibodies levels and YF-specific cellular memory, particularly CMCD4 and EMCD8 as compared to the reference full dose (27,476IU). Although, PRNT seropositivity rates were similar across subgroups (94, 82, 83, 94, 80, and 91%, correspondingly), only doses above 587IU elicited similar iterative proportion of seropositivity rates, calculated as a progressive decrease on seropositivity rates along time (89, 80, 80, and 91%, respectively) as compared to 158IU and 31IU (68 and 46%, respectively). Noteworthy were the strong positive correlations (“EMCD4,EMCD8” and “TNFCD8,IFNCD8”) observed in most subdoses, except for 31IU. Major similarities underscored the preserved antibody titers and the outstanding levels of EMCD8, relevant correlates of protection for YF-specific immunity. These findings provide evidences to support the regular use of dose sparing strategy for YF vaccine in adults.
Highlights
Yellow fever (YF) is a severe acute febrile infectious disease, transmitted by mosquitoes infected with a Flavivirus RNA that occurs in Latin America and Africa
The 8-years followup study demonstrated that volunteers, who had seroconverted upon 17DD-YF primary vaccination with lower doses and had not been revaccinated, still presented
Aiming to determine the overall seropositivity rates achieved by the primary vaccination with lower doses of 17DD-YF vaccine, since the seroconversion at 30–45 days throughout the 8-years time span follow-up, an iterative proportion fitting of plaque reduction neutralization test (PRNT) seropositivity rates was calculated as a progressive decrease on seropositivity rates along time and data presented in the Supplementary Figure 1
Summary
Yellow fever (YF) is a severe acute febrile infectious disease, transmitted by mosquitoes infected with a Flavivirus RNA that occurs in Latin America and Africa. The current outbreaks of YF in Brazil and Africa [5,6,7,8,9,10] have increased the demand for YF vaccine with consequent depletion of international stockpile In response to this scenario, the World Health Organization (WHO) has recommended the use of fractional dose strategy to prevent the YF spread [11, 12]. A relevant issue is whether the immune responses to fractional dose are similar in populations with environmental exposures to other flaviviruses or flavivirus vaccination Another gap refers to the lack of information about the long-term duration of immunogenicity and effectiveness of YF fractional vaccination as compared to the full dose [13]
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