Innovations in HIV-1 Vaccine Design

Jones, Letitia D.; Moody, M. Anthony; Thompson, Amelia B.

PURPOSE: The field of HIV-1 vaccinology has evolved over the last thirty years from the first viral vector-HIV gene insert constructs, to vaccination regimens using a myriad of strategies. These strategies now include germline-targeting, lineage-based, and structure-guided immunogen design. This narrative review outlines the historical context of HIV vaccinology, and subsequently highlights the scientific discoveries over the last six years that promise to propel the field forward. METHODS: We conducted a search of two electronic databases, PubMed® and EMBASE® for experimental studies involving novel HIV immunogen design between 2013 and 2019. During the title and abstract reviews, publications were excluded if they (1) were written in a non-English language and/or (2) were a letter to the editor, a commentary, or a conference only presentation. We then used ClinicalTrials.gov®, to identify completed and ongoing clinical trials using these strategies. FINDINGS: The HIV vaccinology field has undergone periods of significant growth over the last three decades. Findings elucidated in preclinical studies have revealed the importance of the interaction between the cellular and humoral immune system. As a result, several novel rationally-designed vaccine strategies have been developed and explored in the last six years including native-like Env trimers, nanoparticle and mRNA vaccine design strategies among others. Several of these strategies have demonstrated enough promise in animal models to progress toward first-in-human phase 1 clinical trials. IMPLICATIONS: Rapid developments in preclinical and early phase clinical studies suggest that a safe and effective HIV vaccine may be on the horizon.