Long‐Lasting T Cell Responses to Biological Warfare Vaccines in Human Vaccinees

Abstract

Medical countermeasures against biological warfare include the use of vaccines for anthrax and plague, which require repeated dosing and adjuvant to achieve adequate protection from threats such as inhalational anthrax and pneumonic plague. Despite the widespread use of these measures in preparation for recent military deployments, little is known about the cell-mediated immune response that is induced by these vaccines, in comparison with conventional vaccines, such as pertussis or tetanus-diphtheria vaccines. To examine this question, we used cytokine enzyme-linked immunospot assays to measure interferon-gamma, interleukin (IL)-2, IL-4, and IL-13-producing cells in military service personnel vaccinated during the Gulf War of 1990-1991. Our data indicate that 12-15 years after vaccination against anthrax and plague, antigen-specific T cell recall responses are present in the circulation and are comparable in magnitude to those for tetanus-diphtheria toxoids. Recall responses to anthrax were an approximately equal mixture of type 1 T helper cell (interferon-gamma and IL-2) and type 2 T helper cell (predominantly IL-13) responses, whereas plague cellular immunity was more polarized toward type 1 T helper cell responses. Responder cell frequency and type were similar to that against conventional tetanus-diphtheria (mixed type 1 and type 2 T helper cells) vaccine. When veterans were divided according to whether or not they reported multisymptom illness, there was no difference in the frequency or type of cellular response, although the number of cases in each group was small, and these data should be interpreted as preliminary. This study shows that, despite any putative limitations of vaccines for anthrax and plague in terms of achieving protective host immunity, long-lasting cell-mediated responses are generated with these agents.