A vaccine strategy that protects against genital herpes by establishing local memory T cells.
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.
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA.
Haina
H
Shin
Akiko
A
Iwasaki
D000287:Administration, Topical; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002452:Cell Count; D054357:Chemokine CXCL10 / Q000008:administration & dosage; D054370:Chemokine CXCL9 / Q000008:administration & dosage; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000517:prevention & control*; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014611:Vaccination; D014621:Vagina / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D014765:Viral Vaccines