Volume 88, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



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) (ClinicalTrials.gov identifier: NCT00254826).


Article metrics loading...

Loading full text...

Full text loading...



  1. Centers for Disease Control and Prevention, 2012. Health information for international travel. The Yellow Book. New York: Oxford University Press.
  2. Barrett ADT, Teuwen DE, , 2009. Yellow fever vaccine—how does it work and why do rare cases of serious adverse events take place? Curr Opin Immunol 21: 308313.[Crossref]
  3. Martin M, Tsai TF, Cropp B, Chang GJ, Holmes DA, Tseng J, Shieh W, Zaki SR, Al-Sanouri I, Cutrona AF, Ray G, Weld LH, Cetron MS, , 2001. Fever and multiorgan failure associated with 17D-204 yellow fever: a report of four cases. Lancet 358: 98104.[Crossref]
  4. Centers for Disease Control and Prevention (CDC), 2002. Adverse events associated with 17D-derived yellow fever vaccination—United States, 2001–2002. MMWR Morb Mortal Wkly Rep 51: 989993.
  5. Pulendran B, Miller J, Querec TD, Akondy R, Moseley N, Laur O, Glidewell J, Monson N, Zhu T, Zhu H, Staprans S, Lee D, Brinton MA, Perelygin AA, Vellozzi C, Brachman P, Jr Lalor S, Teuwen D, Eidex RB, Cetron M, Priddy F, del Rio C, Altman J, Ahmed R, , 2008. Case of yellow fever vaccine-associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes. J Infect Dis 198: 500507.[Crossref]
  6. Lindsey N, Schroeder BA, Miller ER, Braun MM, Hinckley AF, Marano N, Slade BA, Barnett ED, Brunette GW, Horan K, Staples JE, Kozarsky PE, Hayes EB, , 2008. Adverse event reports following yellow fever vaccination. Vaccine 26: 60776082.[Crossref]
  7. Monath TP, Cetron MS, Teuwen DE, Plotkin SA, Orenstein WA, Offit PA, , 2008. Yellow fever vaccine. , eds. Vaccine, 5th Ed. Philadelphia, PA: Saunders Elsevier, 10951176.
  8. McMahon AW, Eidex RB, Marfin AA, Russell M, Sejvar JJ, Markoff L, Hayes EB, Chen RT, Ball R, Braun MM, Cetron M, , 2007. Neurologic disease associated with 17D-204 yellow fever vaccination: a report of 15 cases. Vaccine 25: 17271734.[Crossref]
  9. Vellozzi C, Mitchell T, Miller E, Casey CG, Eidex RB, Hayes EB, , 2006. Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and corticosteroid therapy: eleven United States cases, 1996–2004. Am J Trop Med Hyg 75: 333336.
  10. Hayes EB, , 2007. Acute viscerotropic disease following vaccination against yellow fever. Trans R Soc Trop Med Hyg 101: 967971.[Crossref]
  11. Martin M, Weld LA, Tsai TF, Mootrey GT, Chen RT, Niu M, Cetron MS, , 2001. Advanced age as a risk factor for illness temporally associated with yellow fever vaccination. Emerg Infect Dis 7: 945951.[Crossref]
  12. Eidex RB, , 2004. History of thymoma and yellow fever vaccination. Lancet 364: 936.[Crossref]
  13. Khromava AY, Eidex RB, Weld LH, Kohl KS, Bradshaw RD, Chen RT, Cetron MS, Yellow Fever Vaccine Safety Working Group; , 2005. Yellow fever vaccine: an updated assessment of advanced age as a risk factor for serious adverse events. Vaccine 23: 32563263.[Crossref]
  14. Kaplan J, Nelson B, Schonberger LB, Hatch MH, Monath TP, Lazuick JS, Calisher CH, Rosa FW, , 1984. The effect of immune globulin on the response to trivalent oral poliovirus and yellow fever vaccinations. Bull World Health Organ 62: 585590.
  15. Theiler M, Whitman L, , 1935. Quantitative studies of the virus and immune serum used in vaccination against yellow fever. Am J Trop Med Hyg 15: 347356.
  16. Sawyer W, Kitchen S, Lloyd W, , 1932. Vaccination against yellow fever with immune serum and virus fixed for mice. J Exp Med 55: 945969.[Crossref]
  17. Monath TP, Nichols R, Archambault WT, Moore L, Marchesani R, Tian J, Shope RE, Thomas N, Schrader R, Furby D, Bedford P, , 2002. Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial. Am J Trop Med Hyg 66: 533534.
  18. Johnson AJ, Martin DA, Karabatos N, Roehrig JT, , 2000. Detection of anti-arboviral immunoglobulin G by using a monoclonal antibody-based capture enzyme-linked immunosorbent assay. J Clin Microbiol 38: 18271831.
  19. Lindsey HS, Calisher CH, Mathews JH, , 1976. Serum dilution neutralization test for California group virus identification and serology. J Clin Microbiol 4: 503510.
  20. Miller JD, van der Most RG, Akondy R, Glidewell JT, Albott S, Masopust D, Murali-Krishna K, Mahar PL, Edupuganti S, Lalor S, Germon S, Del Rio C, Mulligan MJ, Staprans SI, Altman JD, Feinberg MB, Ahmed R, , 2008. Human effector and memory CD8 T cell responses to acute viral infection. Immunity 28: 710722.[Crossref]
  21. Barrett ADT, Pryde A, Medlen AR, Ledger TN, Whitby JE, Gibson CA, DeSilva M, Groves DJ, Langley DJ, Minor PD, , 1989. Examination of the envelope glycoprotein of yellow fever vaccine viruses with monoclonal antibodies. Vaccine 7: 333336.[Crossref]
  22. Johnson BW, Kosoy O, Hunsperger E, Beltran M, Delorey M, Guirakhoo F, Monath T, , 2009. Evaluation of chimeric Japanese encephalitis and dengue viruses for use in diagnostic plaque reduction neutralization tests. Clin Vaccine Immunol 16: 10521059.[Crossref]
  23. Reinhardt B, Jaspert B, Niedrig M, Kostner C, L'age-Stehr J, , 1998. Development of viremia and humoral and cellular parameters of immune activation after vaccination with yellow fever virus strain 17D: a model of human flavivirus infection. J Med Virol 56: 159167.[Crossref]
  24. Monath TP, McCarthy K, Bedford P, Johnson CT, Nicholas R, Yoksan S, Marchesani R, Knauber M, Wells KH, Arroyo J, Guirakhoo F, , 2002. Clinical proof of principle for ChimeriVaxTM: recombinant live, attenuated vaccine against flavivirus infections. Vaccine 20: 10041018.[Crossref]
  25. Wheelock EF, Sibley WA, , 1965. Circulating virus, interferon and antibody after vaccination with the 17-D strain of yellow-fever virus. N Engl J Med 273: 194.[Crossref]
  26. Lang J, Zuckerman J, Clarke P, Barrett P, Kirkpatrick C, Blondeau C, , 1999. Comparison of the immunogenicity and safety of two 17D yellow fever vaccines. Am J Trop Med Hyg 60: 10451050.
  27. Querec T, Bennouna S, Alkan S, Laouar Y, Gorden K, Flavell R, Akira S, Ahmed R, Pulendran B, , 2006. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med 203: 413424.[Crossref]
  28. Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, Kennedy K, Wu H, Bennouna S, Oluoch H, Miller J, Vencio RZ, Mulligan M, Aderem A, Ahmed R, Pulendran B, , 2009. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10: 116125.[Crossref]
  29. Akondy RS, Monson ND, Miller JD, Edupuganti S, Teuwen D, Wu H, Quyyumi F, Garg S, Altman JD, Del Rio C, Keyserling HL, Ploss A, Rice CM, Orenstein WA, Mulligan MJ, Ahmed R, , 2009. The yellow fever vaccine induces a broad and polyfunctional human memory CD8 T cell response. J Immunol 183: 79197930.[Crossref]
  30. Wrammert J, Miller L, Akondy R, Ahmed R, , 2009. Human immune memory to yellow fever and smallpox vaccination. J Clin Immunol 29: 151157.[Crossref]
  31. Centers for Disease Control and Prevention, 2002. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 51 (No. RR-17): 89.

Data & Media loading...

Supplementary Data

Supplementary PDF

  • Received : 20 Mar 2012
  • Accepted : 03 Sep 2012

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error