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