Development of targeted adjuvants for HIV-1 vaccines
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AIDS Research and Therapy Open Access
REVIEW
Development of targeted adjuvants for HIV‑1 vaccines Jun Liu1* and Mario Ostrowski1,2,3*
Abstract Finding new adjuvants is an integrated component of the efforts in developing an effective HIV-1 vaccine. Compared with traditional adjuvants, a modern adjuvant in the context of HIV-1 prevention would elicit a durable and potent memory response from B cells, CD8+ T cells, and NK cells but avoid overstimulation of HIV-1 susceptible CD4+ T cells, especially at genital and rectal mucosa, the main portals for HIV-1 transmission. We briefly review recent advances in the studies of such potential targeted adjuvants, focusing on three classes of molecules that we study: TNFSF molecules, TLRs agonists, and NODs agonists. Keywords: HIV, Vaccine, Adjuvant, TNFSF, TLRs, NODs Background More than three decades after human immunodeficiency virus 1 (HIV-1) was identified as the cause of AIDS, we still do not have an effective vaccine to stymie its global spread [1]. Barriers to developing an effective HIV-1 vaccine include the following: (1) HIV-1 mutates rapidly and has a tremendous genetic diversity. In this regard, broadly neutralizing antibodies (bNAbs) can neutralize a broad range of HIV-1 isolates, but we do not know how to induce such bNAbs with a vaccine [2]. Vaccines that induce non-broadly neutralizing HIV-1 Env-binding antibodies can afford partial protection against HIV-1/ SHIV infection, but their efficacy needs to be substantially improved for clinical use [3, 4]. (2) All HIV-1 envelope (Env) based vaccine candidates can only induce a short-lived antibody response. This is in striking contrast to vaccines currently in clinical use and may severely limit the long-term efficacy of HIV-1 vaccines [5–8]. The mechanisms underlying this short duration of Envantibody responses are not clear yet, but might be due to the failure of the Env glycoprotein to induce long-lived plasma cells [9, 10]. (3) HIV-1 is a rapidly replicating lentivirus that can establish latent infection soon after
*Correspondence: [email protected]; [email protected] 1 Clinical Sciences Division, University of Toronto, Room 6352, Medical Sciences Building, 1 King’s College Circle, Toronto, ON M5S1A8, Canada Full list of author information is available at the end of the article
infection [11]. Thus an effective HIV-1 vaccine should elicit memory immune responses that can be mobilized fast (probably within a few days of infection) and sufficiently to block HIV-1 transmission through genital and rectal mucosa. Cytomegalovirus (CMV)-vectored HIV-1 vaccine might be able to elicit such a persistent and strong immune response [12], but we do not know if and how other vaccine platforms can elicit such immune responses, especially at genital and rectal mucosa. (4) CD4+ T cells play a pivotal role in forming memory immune response but are also target cells of HIV-1. An effective HIV-1 vaccine should induce potent cellular and humoral memory immune responses but avoid or limit stimulation of HIV-1 suscep
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