Excerpt from Commentary, Journal of Investigative Dermatology
Excerpt from Commentary, Journal of Investigative Dermatology (2008) 128, 2353–2354. doi:10.1038/jid.2008.221; Acne Vaccines: Therapeutic Option for the Treatment of Acne Vulgaris?
Jenny Kim, Division of Dermatology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA, and Department of Dermatology, Greater Los Angeles Healthcare System Veterans Affairs, Los Angeles, California, USA
Many of the current therapies focus on reducing the number of P. acnes organisms, and most recent developments have been in the use of combination therapies. Benzoyl peroxide and the retinoids have been added to topical antibiotics with the hope that the frequency of resistance will decrease, thereby improving the therapeutic outcome. On the other hand, only a few therapies focus primarily on reducing inflammation. The use of lower doses of antibiotics for their anti-inflammatory properties is currently being evaluated. In addition, recent studies suggest that in addition to its well-known effect on “normalizing” the follicular epithelium, retinoic acid demonstrates anti-inflammatory and antimicrobial effects (Liu et al., 2005, 2008), underscoring the need to investigate further the immunomodulatory effects of acne therapies. Despite substantial interest in basic acne research, acne vaccines that modulate host immune responses to P. acnes are not available.
In the study reported in this issue, Nakatsuji et al. (2008b) generated antibodies using inactivated P. acnes, postulating that they might provide protective immunity. The authors demonstrated that intranasal immunization of mice with this inactivated vaccine generated in vivo protective immunity against P. acnes challenge. Specifically, the antibodies elicited by inactivated P. acnes attenuated IL-8 production in human sebocytes; however, there was no effect on P. acnes growth. The clinical improvement observed in this P. acnes inflammatory murine model suggests that for acne treatment, antibodies that primarily exhibit anti-inflammatory properties might be sufficient for clinical improvement but without an antimicrobial effect.
Immunization with P. acnes holds promise for acne therapy.
The inactivated P. acnes vaccine used in this study targeted the whole bacterium, most likely without specificity. Therefore, developing vaccines against specific P. acnes antigens might be even more useful, as previously demonstrated by the same research group (Nakatsuji et al., 2008a). This would require that P. acnes antigens first be identified and then characterized for the types of response that each antigen elicits; this information could then be used to develop a component acne vaccine. Very few P. acnes antigens have been identified and studied.
It will be important to evaluate the antibodies generated against P. acnes for other immunomodulatory effects, including their ability to induce proinflammatory mediators and cytotoxicity, which might lead to tissue injury. It has been shown that some patients have antibodies against P. acnes, and positive correlations between antibody titers and the severity of the disease have been reported (Webster et al., 1985; Ingham et al., 1987; Ashbee et al., 1997). Thus, not all antibodies directed against P. acnes may be beneficial, and they may even worsen the disease.
Part of the difficulty in developing any acne therapy is that there is no perfect animal model. Although the mouse model used by Nakatsuji et al. (2008b) demonstrated a decrease in ear swelling in vaccinated mice, the lesions produced by injection of P. acnes into the ears of mice do not reproduce clinical acne lesions exactly. For this reason, it is not certain that similar clinical improvement will occur in humans, in whom other varying factors, such as the presence of inflammatory lipids in sebum, may influence the growth and behavior of P. acnes. Nonetheless, the authors of this study offer an important and interesting concept—that focusing on attenuating the inflammatory component of the disease could be therapeutically beneficial. Because the induction of cytokines, chemokines, and metalloproteinases by P. acnes occurs via a Toll-like receptor 2 (TLR2)-dependent pathway, the development of vaccines or other immune therapies that target TLR2 and other TLRs may provide other alternatives to conventional therapy. We are already familiar with agents that modulate TLR response, such as imiquimod, which enhances TLR7 and TLR8 function, and retinoic acid, which downregulates TLR2 expression and function, suggesting that vaccines with potent anti-TLR immunity may hold promise for the future of acne therapy.