Subcutaneous Administration of a Recombinant Vaccinia Virus Vaccine Expressing Multiple Envelopes of HIV-1

  • K. S. Slobod
  • T. D. Lockey
  • N. Howlett
  • R. V. Srinivas
  • S. D. Rencher
  • P. J. Freiden
  • P. C. Doherty
  • J. L. Hurwitz
Article

Abstract

A critical goal of HIV vaccine development is the identification of safe and immunogenic vectors. Recombinant vaccinia virus is a highly effective vaccine vector, with demonstrated capacity to protect animals from various viral pathogens, including rabies. Unlike many other candidate vaccine vectors, vast human experience exists with the parenteral smallpox vaccine. However, consideration of recombinant vaccinia virus as a modern vaccine is complicated by the relatively high prevalence of immunocompromised persons compared to such prevalence 4 or more decades ago (when smallpox vaccination was still routine). Administering vaccine by the subcutaneous (SQ) route, rather than the traditional scarification route, could address these concerns. SQ administration could prevent transmission of vaccinia virus to potentially vulnerable persons; it could also avoid the most common adverse events, which are cutaneous in nature. However, previous studies suggest that elicitation of immune response against passenger gene products following SQ administration requires development of a superficial pox lesion, defeating the intention of SQ administration. This is the first report to demonstrate that SQ administration of recombinant vaccinia virus does elicit immune response to the passenger protein in the absence of a cutaneous pox lesion. Results further show that a multi-envelope HIV vaccine can elicit antibody responses toward heterologous HIV-1 not represented by primary sequence in the vaccine. These findings have global implications because they support the consideration of recombinant vaccinia virus as a valuable HIV vaccine vector system.

Notes

Acknowledgements

Sources of financial support: P01 AI45142 (NIAID, NIH for KSS, PCD and JLH). This work was supported in part by Cancer Center Support Grant No P30-CA21765 (NCI) and the American Lebanese Syrian Associated Charities (ALSAC). TDL was supported by a national Research Service Award 5T32-CA09346. We thank B. Williams, M. Roy, J. Parobek and J. Zacher for their assistance; W.T. Hughes and J.W. Sixbey, P.M. Flynn for helpful discussion. We thank H. Stamey and the Tennessee Blood Service (Memphis, TN). We thank the NIH AIDS Research and Reference Reagent Repository and WHO/UNAIDS for providing envelope genes representative of different clades. We are grateful to the volunteers without whom the study would not have been possible.

References

  1. 1.
    Lockey TD, Slobod KS, Caver TE, D’Costa S, Owens RJ, McClure HM, Compans RW, Hurwitz JL (2000) Multi-envelope HIV vaccine safety and immunogenicity in small animals and chimpanzees. Immunol Res 21:7–21CrossRefPubMedGoogle Scholar
  2. 2.
    Caver TE, Lockey TD, Srinivas RV, Webster RG, Hurwitz JL (1999) A novel vaccine regimen utilizing DNA, vaccinia virus and protein immunizations for HIV-1 envelope presentation. Vaccine 17:1567–1572CrossRefPubMedGoogle Scholar
  3. 3.
    Hammarlund E, Lewis MW, Hansen SG, Strelow LI, Nelson JA, Sexton GJ, Hanifin JM, Slifka MK (2003) Duration of antiviral immunity after smallpox vaccination. Nat Med 9:1131–1137CrossRefPubMedGoogle Scholar
  4. 4.
    Centers for Disease Control and Prevention (2003) Smallpox vaccination and adverse reactions: guidance for clinicians. MMWR Dispatch 52:1–29Google Scholar
  5. 5.
    Graham BS, Belshe RB, Clements ML, et al (1992) Vaccination of vaccinia-naïve adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. J Infect Dis 166:244–252PubMedGoogle Scholar
  6. 6.
    Rencher SD, Slobod KS, Dawson D, Lockey TD, Hurwitz JL (1995) Does the key to a successful HIV vaccine lie among the envelope sequences of infected individuals? AIDS Res Hum Retroviruses 11:1131–1133PubMedGoogle Scholar
  7. 7.
    Rencher SD, Hurwitz JL (1997) Effect of natural HIV-1 envelope V1-V2 sequence diversity on the binding of V3 and non-V3-specific antibodies. J Acquir Immune Defic Syndr 16:69–73Google Scholar
  8. 8.
    Ryan KW, Owens RJ, Hurwitz JL (1997) Preparation and use of vaccinia virus vectors for HIV protein expression and immunization. In: Lefkovits I (ed) Immunology methods manual. Academic Press, New York, pp 1993–2015Google Scholar
  9. 9.
    Cieslak TJ, Christopher GW, Kortepeter MG, et al (2000) Immunization against potential biological warfare agents. Clin Infect Dis 30:843–850CrossRefPubMedGoogle Scholar
  10. 10.
    McClain DJ, Harrison S, Yeager CL, et al (1997) Immunologic responses to vaccinia vaccines administered by different parenteral routes. J Infect Dis 175:756–763PubMedGoogle Scholar
  11. 11.
    Connors JD, McIntosh K, Cherry JD, et al (1977) Primary subcutaneous vaccination. J Infect Dis 135:167–175PubMedGoogle Scholar
  12. 12.
    Cooney EL, Collier AC, Greenberg PD, et al (1991) Safety of immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet 337:567–572CrossRefPubMedGoogle Scholar
  13. 13.
    Slobod KS, Rencher SD, Farmer A, Smith FS, Hurwitz JL (1994) HIV type 1 envelope sequence diversity in an inner city community. AIDS Res Hum Retroviruses 10:873–875PubMedGoogle Scholar
  14. 14.
    Moore JP, Ho DD (1993) Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J Virol 67:863–875PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • K. S. Slobod
    • 1
    • 3
  • T. D. Lockey
    • 2
  • N. Howlett
    • 1
  • R. V. Srinivas
    • 1
    • 5
  • S. D. Rencher
    • 2
    • 6
  • P. J. Freiden
    • 1
  • P. C. Doherty
    • 2
    • 4
  • J. L. Hurwitz
    • 2
    • 4
  1. 1.Department of Infectious DiseasesSt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of ImmunologySt. Jude Children’s Research HospitalMemphisUSA
  3. 3.Department of PediatricsUniversity of TennesseeMemphisUSA
  4. 4.Department of PathologyUniversity of TennesseeMemphisUSA
  5. 5.NIH, NIAID, CSRBethesdaUSA
  6. 6.LamarUSA

Personalised recommendations