HIV Vaccines 2023
Human Immunodeficiency Virus (HIV) vaccine development has accelerated in 2023, with candidates utilizing innovative technologies such as mRNA. According to the U.S. National Institutes of Health (NIH), HIV vaccine candidates can not cause an HIV infection. And the NIH published an article: Progress toward an HIV vaccine. The development of a preventive vaccine against HIV represents the best solution for controlling and eradicating the HIV pandemic, says the Vaccine Research Institute.
Developing HIV vaccines requires various clinical trials: phase 1, phase 2, phase 3, and phase 4. Each development step is essential, and all stages need people to participate, who may be compensated. On February 24, 2023, HIV.gov spoke with Dr. Dieffenbach, who noted that while there won't be an HIV vaccine in the near term, he encouraged anyone interested in learning about current HIV vaccine clinical trials to visit the HVTN website.
The National Institute of Allergy and Infectious Diseases (NIAID) will host the sixth biennial Strategies for an HIV Cure meeting on October 12-13, 2023. The NIH's Carl Dieffenbach, Ph.D. spoke with Louis Shackelford, MPH, at the International AIDS Society's 12th Conference on HIV Science about HIV vaccine studies and the potential roles for broadly neutralizing antibodies (bNAbs), which may also activate other immune cells to help destroy HIV-infected cells. As of September 23, 2023, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had not approved an HIV prevention vaccine. However, people with HIV are recommended to receive two doses of the MenACWY vaccine.
HIV Vaccine Candidates 2023
Following the discovery of HIV as a causative agent of AIDS, multiple HIV vaccine clinical trials have been conducted globally over the past 35 years. The use of nanotechnology in the design and improvement of HIV vaccines has recently advanced.
eOD-GT8 60mer (mRNA-1644) - Developed by scientific teams at IAVI and Scripps Research and delivered via Moderna's mRNA platform. Recent findings from the Phase I clinical trial IAVI G001 showed that vaccination with the HIV immunogen eOD-GT8 60mer as a recombinant protein vaccine safely induced the targeted immune responses in 97% of recipients. A phase 1 clinical study (IAVI G002) established clinical proof of concept for the germline-targeting vaccine design priming strategy, supporting the development of boosting regimens to generate VRC01-class bnAb responses against HIV. A third Phase 1 clinical study (IAVI G003) is also underway. The hypothesis is that the eOD-GT8 60mer mRNA Vaccine as a "germline-targeting" immunogen will generate detectable VRC01-class IgG B-cells in the African populations. Findings from the G001 study, the first of its kind, were published in Science on December 2, 2022.
Moderna Inc. is advancing three Phase I clinical trials of HIV vaccines with partners (mRNA-1644/IAVI G002; mRNA-1644/IAVI G003; mRNA-1574/NIAID). mRNA-1574 is participating in the U.S. NIH's HVTN 302 study, there are three vaccine candidates: 1) BG505 MD39.3 mRNA, 2) BG505 MD39.3 gp151 mRNA, and 3) BG505 MD39.3 gp151 CD4KO mRNA.
Vir Biotechnology, Inc. is developing VIR-1388, an investigational novel T-cell vaccine for the prevention of HIV based on the human cytomegalovirus vector (CMV) platform. This means a weakened version of CMV delivers the HIV vaccine material to the immune system without causing disease in the study participants. The phase 1 clinical trial is partly funded by the Bill and Melinda Gates Foundation and the National Institutes of Health's Division of AIDS through the HIV Vaccine Trials Network. The U.S. NIAID has provided scientific and financial support throughout the lifecycle of a novel vaccine known as VIR-1388. The first participant was dosed in a Phase 1 trial in September 2023, and the Company expects initial data in the second half of 2024.
HOOKIPA Pharma - Arenaviral therapeutic vaccines showed in a nonhuman, preclinical setting that 2-vector therapy induces a greater immune response than single-vector therapy and significantly reduces viral load.
AELIX Therapeutics S.L. - The therapeutic HIV vaccine, HIVACAT T-cell immunogen, is a novel human immunodeficiency virus (HIV) vaccine immunogen that leads to a prolonged period without Antiretroviral Treatment and supports the use of HTI vaccine for combination cure strategies for HIV. Positive results from the phase 1 clinical study AELIX-002 published in the journal Nature Medicine.
CD40.HIVRI.Env is a vaccine candidate conducting a phase 1 clinical study and was developed by the Vaccine Research Institute (ANRS and Université Paris-Est Créteil, France) with a technology whose exclusive worldwide license is held by LinKinVax. On February 22, 2023, LinkinVax announced the observed counts of CD4+ T cells targeting specifically the HIV envelope protein produced after the vaccination remained stable until Week 48.
Uvax Bio, LLC announced the U.S. NIH agreed to sponsor its HIV-1 vaccine candidate in a Phase 1 clinical trial to launch in the first quarter of 2024. In addition, research (April 2023) reported a single-component, self-assembling protein nanoparticle (1c-SApNP) could display 8 or 20 native-like Env trimers as vaccine candidates.
HIV Monoclonal Antibody
Trogarzo® (ibalizumab) is a monoclonal antibody antiretroviral therapy associated with favorable virologic outcomes used in routine care in heavily treatment-experienced people with HIV in a study posted in May 2023. Trogarzo is a long-acting, CD4-directed, post-attachment HIV-1 inhibitor.
The peer-reviewed journal Nature published a study on June 1, 20,22 that concluded two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074, completely suppressed HIV for about 40 weeks in patients who participated in a U.S. government-funded phase 1 clinical trial. The findings suggest that future antibody therapies may offer effective HIV treatment for extended periods without antiretroviral therapy.
Leronlimab, a CCR5 antagonist IgG4 monoclonal antibody, is designed to bind to C-C chemokine receptor type 5 (CCR5), a protein on the surface of specific immune system cells believed to play a role in numerous disease processes, including HIV.
A small phase I clinical trial led by Massachusetts General Hospital has tested an anti-HIV strategy involving an adeno-associated viral vector-based gene delivery system that instructs cells to pump out antibodies that block HIV. The treatment was safe and well-tolerated in the trial of eight adults with HIV. In addition, all participants produced measurable amounts of anti-HIV antibodies in their blood as of April 11, 2022.
ViiV Healthcare N6LS is a broadly neutralizing antibody that works by binding to a specific site (gp120) on the surface of HIV, preventing its entry into immune system cells (CD4+ T-cells). By blocking HHIV'sentry into human CD4+ cells, the virus cannot replicate, and the HIV transmission process may be prevented.
HIV and COVID-19 Vaccination
The International Journal of Infectious Diseases published on October 12, 2022: Pubmed/Medline, EMBASE, and the Cochrane Library were searched, finding 22 studies with 6,522 people living with HIV (PLWH) subjects who met the study inclusion criteria. COVID-19 vaccines showed favorable immunogenicity and efficacy in PLWH. A second dose is associated with consistently improved seroconversion, although it is slightly lower in PLWH t in healthy individuals. Additional strategies, such as a booster vaccination with mRNA COVID-19 vaccines, might improve seroprotection for these patients.
Sexually Transmitted Disease Vaccines
The sexually transmitted disease vaccine summary was updated in September 2023.
HIV Treatment 2023
In August 2023, the U.S. Preventive Services Task Force recommended that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV. The U.S. FDA-approved Apretude (cabotegravir extended-release injectable suspension) for use in at-risk adults and adolescents weighing at least 35 kilograms for preexposure prevention to reduce the risk of sexually acquired HIV on December 20, 2021. According to an editorial published in JAMA Internal Medicine, cabotegravir can be taken once every two months.
EDURANT® is a human immunodeficiency virus type 1 (HIV-1) specific, nonnucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve patients 12 years of age and older and weighing at least 35 kg with HIV-1 RNA less than or equal to 100,000 copies/mL.
Gilead Sciences, Inc. announced on December 22, 2022, that Sunlenca® (lenacapavir), in combination with other antiretroviral, was Approved by the U.S. FDA for the treatment of HIV-1 infection in heavily treatment-experienced adults with multi-drug resistant HIV-1 infection. Sunlenca offers a twice-yearly treatment option for adults with HIV that their current treatment regimen does not adequately control. In May 2022, the NEJM published an ORIGINAL ARTICLE: Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.
Gilead Sciences, Inc. announced on February 22, 2023, data evaluating lenacapavir in combination with broadly neutralizing antibodies (bNAbs) teropavimab and zinlirvimab as a potential long-acting treatment regimen with twice-yearly dosing. Results from the Phase 1b clinical trial demonstrated the investigational combination was generally well tolerated with high efficacy in select virologically suppressed participants living with HIV. The combination of lenacapavir with teropavimab and zinlirvimab will advance to a Phase 2 study in 2023 in virologically suppressed people with HIV.
The UB-421 SC formulation Semzuvolimab is in Phase 2 clinical trial development for HIV treatment, Last Update was Posted on February 23, 2023, with an Estimated Study Completion Date of December 31, 2025. The study protocol is entitled: Single arm Open-Label Phase 2 Trial of anti-CD4 Antibody UB-421 in Combination with Optimized Background Antiretroviral Therapy in Patients with Multi-Drug Resistant HIV-1 InfectThe NIAID/NIH sponsors this trialD/NIH. It was developed to provide a convenient delivery method compared to the IV route so patients can self-administer the medication.
