A vaccine strategy protects against genital herpes by establishing local memory T cells

By Haina Shin, A. Iwasaki. Nature, 2012

617 citations recorded by the source corpus.

Most successful existing vaccines rely on neutralizing antibodies, which may not require specific anatomical localization of B cells. However, efficacious vaccines that rely on T cells for protection have been difficult to develop, as robust systemic memory T-cell responses do not necessarily correlate with host protection. In peripheral sites, tissue-resident memory T cells provide superior protection compared to circulating memory T cells. Here we describe a simple and non-inflammatory vaccine strategy that enables the establishment of a protective memory T-cell pool within peripheral tissue. The female genital tract, which is a portal of entry for sexually transmitted infections, is an immunologically restrictive tissue that prevents entry of activated T cells in the absence of inflammation or infection. To overcome this obstacle, we developed a vaccine strategy that we term ‘prime and pull’ to establish local tissue-resident memory T cells at a site of potential viral exposure. This approach relies on two steps: conventional parenteral vaccination to elicit systemic T-cell responses (prime), followed by recruitment of activated T cells by means of topical chemokine application to the restrictive genital tract (pull), where such T cells establish a long-term niche and mediate protective immunity. In mice, prime and pull protocol reduces the spread of infectious herpes simplex virus 2 into the sensory neurons and prevents development of clinical disease. These results reveal a promising vaccination strategy against herpes simplex virus 2, and potentially against other sexually transmitted infections such as human immunodeficiency virus.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/e4aee49ee8730880df17152711ba3cc79ffb6912

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Citations in the corpus

Human T cell development, localization, and function throughout life (2018, background): “The clinical importance of Trm cells is also underscored by the fact that mouse Trm cells can be generated in response to vaccines, non-infectious allergens, autoantigens, and tumors (Hondowicz et al., 2016; Morawski et al., 2017; Shin and Iwasaki, 2012; Zens et al., 2016).”
Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites (2017, background): “Mouse models have also demonstrated the feasibility of targeting TRMs in vaccines for generating protective immunity (Shin and Iwasaki, 2012; Zens et al., 2016).”
Quantifying memory CD8 T cells reveals regionalization of immunosurveillance (2015, background): “These observations revise perceptions of immunosurveillance and may help explain why frontline memory CD8 T cell populations can rapidly detect infections in barrier tissues (Gebhardt et al., 2009; Jiang et al., 2012; Shin and Iwasaki, 2012; Teijaro et al., 2011; Wu et al., 2014).”
Tissue-Resident Memory T Cells (2014, background): “For instance, a larger number of Trm cells within the female reproductive tract are induced to express aeb7 after local inflammation compared to systemic infection or in the presence of local inflammation (Çuburu et al., 2012; Li et al., 2008; Mackay et al., 2012; Shin and Iwasaki, 2012).”