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BOX 2.2 EXPERIMENTS Dermal damage increases immunity and host survival

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When it was still in use, the smallpox vaccine was delivered by a bifurcated (two-pronged) needle in a process referred to as scarification. Vaccination resulted in local damage to the skin and a subsequent (though quickly re solved) lesion in most individuals that often left a lifelong scar. Until recently, it was not appreciated that the scarification process itself was an important component of the vaccine’s efficacy. Experiments using the smallpox-related virus vaccinia virus showed that intra dermal inoculation of the virus into rabbits resulted in lethal disease by 8 days after infection, whereas delivery by scarification led to a protective host response and animal survival. Scarified rabbits also responded immunologically earlier than those inoculated by the intradermal route. Moreover, scarification in the absence of virus, followed immediately by a same-site intradermal challenge with virus, resulted in significant protection to the infected rabbits. This dramatic difference can be attributed to the rapid induction of a nonspecific host response caused by the scarification wound itself. Scarification damages skin cells and the underlying epidermis, inducing the release of cytokines and chemokines that help direct the host’s immune response to the site of infection and restrict the dissemination of the virus throughout the host.

 Rice AD, Adams MM, Lindsey SF, Swetnam DM, Manning BR, Smith AJ, Burrage AM, Wallace G, MacNeill AL, Moyer RW. 2014. Protective properties of vaccinia virus-based vaccines: skin scarification promotes a nonspecific immune response that protects against orthopoxvirus disease. J Virol 88:7753–7763.



Figure 2.6 Sites of viral entry in the respiratory tract. (Left) A detailed view of the respiratory epithelium. A layer of mucus, produced by goblet cells, is a formidable barrier to virus particle attachment. Virus particles that traverse this layer may reproduce in ciliated cells or pass between them, reaching another physical barrier, the basement membrane. Beyond this extra cellular matrix are tissue fluids, from which particles may be taken into lymphatic capillaries and reach the blood. Local macrophages patrol the tissue fluids in search of foreign particles. (Right) Viruses that reproduce at different locations within the respiratory tract, noted with the associated clinical syndromes. SARS, severe acute respiratory syndrome; MERS, Middle East respiratory syndrome. Adapted from Mims CA et al. 1995. Mims’ Pathogenesis of Infectious Disease (Academic Press, Orlando, FL).

Principles of Virology, Volume 2

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