Scientific Publications by FDA Staff

J Infect Dis 2005 Feb 1;191(3):372-81

Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.

Edghill-Smith Y, Bray M, Whitehouse CA, Miller D, Mucker E, Manischewitz J, King LR, Robert-Guroff M, Hryniewicz A, Venzon D, Meseda C, Weir J, Nalca A, Livingston V, Wells J, Lewis MG, Huggins J, Zwiers SH, Golding H, Franchini G.

Franchini G, NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA NCI, Immune Biol Retroviral Infect Sect, Bethesda, MD 20892 USA NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA So Res Inst, Frederick, MD USA

It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals.