Killed but metabolically active vaccines
Beginning in the 20th century and continuing into the new millennia, vaccines against numerous diseases have had an unquestioned principal role of both enhancing the quality of life and increasing life expectancy (Rappuoli R, Mandl CW, Black S, De Gregorio E: Vaccines for the twenty-first century society. Nat Rev Immunol 2011, 11:865–872). Despite this success and the development of sophisticated new vaccine technologies, there remain multiple infectious diseases including tuberculosis, malaria and AIDS that await an effective prophylactic vaccine. In addition, there have been recent clinical successes among individuals with cancer using vaccine treatment strategies — so-called therapeutic vaccines — that stimulate tumor specific immunity and increase survival (Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, et al.: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Engl J Med 2010, 363:411–422). Here we summarize a new class of vaccines termed Killed But Metabolically Active (KBMA). KBMA vaccines are whole pathogenic or attenuated organisms killed through photochemical inactivation and cannot cause disease, yet retain sufficient metabolic activity to initiate a potent immune response. KBMA vaccines have two broad applications. First, recombinant KBMA vaccines encoding selected antigens relevant to infectious disease or cancer can be used to elicit a desired immune response. In the second application, KBMA vaccines can be derived from attenuated forms of a targeted pathogen, allowing for the presentation of the entire antigenic repertoire to the immune system, of particular importance when the correlates of protection are unknown.
Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (209 K)Download as PowerPoint slideHighlights► KBMA vaccines are whole photochemically inactivated organisms and cannot cause disease yet retain metabolic activity. ► KBMA vaccines lack nucleotide excision repair and are exquisitely sensitive to inactivation by psoralen and UVA light. ► KBMA vaccines can encode recombinant antigens relevant to infectious disease or cancer. ► KBMA vaccines derived from an attenuated selected pathogen present the entire antigenic repertoire to the immune system. ► The KBMA technology can also be used to generate vaccine candidates from protozoan pathogens such as Leishmania species.
Journal: Current Opinion in Biotechnology - Volume 23, Issue 6, December 2012, Pages 917–923