An Update on the HIV DNA Vaccine Strategy

Abstract

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable side effects such as lipodystrophy and endocrine dysfunctions, which result in HAART intolerability. HAART is also not curative. Furthermore, new HIV infections continue to occur globally at a high rate, with an estimated 1.7 million new infections occurring in 2018 alone. Therefore, there is still an urgent need for an affordable, effective, and readily available preventive vaccine against HIV/AIDS. Despite this urgent need, however, progress toward an effective HIV vaccine has been modest over the last four decades. Reasons for this slow progress are mainly associated with the unique aspects of HIV itself and its ability to rapidly mutate, targeting immune cells and escape host immune responses. Several approaches to an HIV vaccine have been undertaken. However, this review will mainly discuss progress made, including the pre-clinical and clinical trials involving vector-based HIV DNA vaccines and the use of integrating lentiviral vectors in HIV vaccine development. We concluded by recommending particularly the use of integrase-defective lentiviral vectors, owing to their safety profiles, as one of the promising vectors in HIV DNA vaccine strategies both for prophylactic and therapeutic HIV vaccines.

Prophylactic Ribonucleic Acid Vaccines to Combat RNA Viral Infections in Humans

“…These clinical trials were successful in phases 1 and 2; however, they were stopped in mid-phase 3 for futility by Data Safety Monitoring Board (DSMB) [32]. DSMB data analysis study did not find a statistically significant decrease in the number of HIV infections in the vaccine compared to placebo groups [33]. It was determined that the elicitation of humoral immune response was not robust enough to prevent infection or stop the progression of AIDS [34].…”

“…Numerous recombinant DNA-based vaccines were tested against several immunogenic epitopes (e.g., HIV protease, gag, env, gp120/140, or reverse transcriptase proteins) [35][36][37]. Various routes of administration (mucosal, intradermal, intravenous, and intramuscular) were also tested [33], and intramuscular injections were found to be the most efficacious. Recombinant DNA-based HIV vaccines generated only modest HIV-specific T cell and humoral responses, and that was insufficient for protection [38,39].…”

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

“…In addition, there are also other types of vaccines like DNA vaccines ( 130 , 131 ) or VLV vaccines (virus like vaccines) ( 132 ). Clinical trials have also shown that the current generation of DNA vaccines cannot induce a strong antibody response.…”

Crossroads of Drug Abuse and HIV Infection: Neurotoxicity and CNS Reservoir

“…Antiretroviral neurotoxicity, HIV persistence, transient HIV replication in the CNS, inflammation, mitochondrial dysfunction, and autophagy all contribute to the pathology of HAND [20,21]. Naturally occurring or acquired comorbid diseases and conditions cause further complications.…”