HIV/AIDS Vaccines: 2018

Abstract

Human immunodeficiency virus (HIV) has infected 76 million people and killed an estimated 35 million. During its 40-year history, remarkable progress has been made on antiretroviral drugs. Progress toward a vaccine has also been made, although this has yet to deliver a licensed product. In 2007, I wrote a review, HIV AIDS Vaccines: 2007. This review, HIV AIDS Vaccines: 2018, focuses on the progress in the past 11 years. I begin with key challenges for the development of an AIDS vaccine and the lessons learned from the six completed efficacy trials, only one of which has met with some success.

Figure 1

Timeline for human immunodeficiency virus (HIV) vaccine efficacy trials. Years at the top are for 4‐year intervals, individual years are designated by dotted lines. Ad5, adenovirus serotype 5 vector; Ad26, adenovirus serotype 26 vector; ALVAC, canarypox vector; HVTN, HIV Vaccine Trials Network; IVDU, intravenous drug users; MSM, men who have sex with men; RSA, Republic of South Africa; TGSM, male to female transgender individuals who have sex with men; US, United States; VCP, canary pox vector.

Figure 2

Functional regions of antibody and the human immunodeficiency virus (HIV) envelope. (a) Schematic of an antibody (Ab) showing variable Fab and conserved Fc regions. Fab and Fc fragments are generated by papain cleavage: Fab is the variable antigen binding fragment, and Fc is the crystallizable constant fragment. (b) Schematic of the HIV envelope glycoprotein (Env) with receptor binding (gp120) and transmembrane proteins (gp41) indicated. nAb, neutralizing Ab; pnnAb, protective non‐neutralizing Ab. Schematic of immunoglobulin G (IgG) is reproduced from commons.wikimedia.org by Gareth White and is licensed under CC BY 2.0. Schematic of HIV Env is reproduced with permission from David H. Spach, MD and the National HIV Curriculum.

Figure 3

Comparison of the activities of broadly neutralizing antibodies (bnAbs) and protective non‐neutralizing antibodies (pnnAbs). Cʹ, complement.

Figure 4

Schematics for forms of the human immunodeficiency virus (HIV) envelope glycoprotein (Env) being developed and used for immunizations. Ab, antibody; bnAb, broadly neutralizing antibody; C1, constant region 1 of gp120; IDR, highly conserved immunodominant region of gp41; nAb, neutralizing antibody; pnnAb, protective non‐neutralizing Ab; SOSIP, disulfide stabilized, cleaved trimeric form of gp140; T/F, transmitted founder virus for an infection; V1V2, variable loops one and two that form the apex of the HIV Env; V3, variable loop 3 of the HIV gp120; VLP, virus‐like particle. Parallel blue line, viral or plasma membrane. See text for more information and references.