A randomized, double-blind, controlled trial of the 17D yellow fever virus vaccine given in combination with immune globulin or placebo: comparative viremia and immunogenicity

Abstract

We evaluated whether coadministration of the yellow fever (YF) virus vaccine with human immunoglobulin (Ig) that contained YF virus-neutralizing antibodies would reduce post-vaccination viremia without compromising immunogenicity and thus, potentially mitigate YF vaccine-associated adverse events. We randomized 80 participants to receive either YF vaccine and Ig or YF vaccine and saline placebo. Participants were followed for 91 days for safety and assessments of viremia and immunogenicity. There were no differences found between the two groups in the proportion of vaccinated participants who developed viremia, seroconversion, cluster of differentiation (CD)-8(+) and CD4(+) T-cell responses, and cytokine responses. These results argue against one putative explanation for the increased reporting of YF vaccine side effects in recent years (i.e., a change in travel clinic practice after 1996 when hepatitis A prophylaxis with vaccine replaced routine use of pre-travel Ig, thus potentially removing an incidental YF vaccine-attenuating effect of anti-YF virus antibodies present in Ig).

Trial registration: ClinicalTrials.gov NCT00254826.

Figure 1.

17D YF vaccine-induced viremia (measured by RT-PCR) on post-vaccination days 0–14.

Figure 2.

Proportion of seroconverters and their PRNT₉₀ titers after immunization with the 17D YF vaccine.

Figure 3.

Activated CD8⁺ T cells after immunization with 17D YF vaccine and Ig or saline.

Figure 4.

Activated CD4⁺ T cells after immunization with 17D YF vaccine and Ig or saline.