HIV Vaccines March 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 eventual HIV vaccine, on December 13, 2022.
The development of a preventive vaccine against HIV represents the best solution for controlling and eradicating the HIV pandemic, says the Vaccine Research Institute. HIV.gov spoke with Dr. Carl Dieffenbach, Director of the Division of AIDS at NIH's National Institute of Allergy and Infectious Disease, on February 24, 2023. Dr. Dieffenbach 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.
As of March 13, 2023, the U.S. Food and Drug Administration (FDA) had not approved an HIV prevention vaccine.
HIV Vaccine Candidates March 2023
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 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.
mRNA-1574 - Produced by Moderna Inc. and 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. Each investigational vaccine is designed to present the spike protein on the surface of HIV that facilitates entry into human cells and encodes for different but highly related stabilized proteins.
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 (HT,I) is a novel human immunodeficiency virus (HIV) vaccine immunogen, leads to a prolonged period without Antiretroviral Treatment (ART) 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. It is the first vaccine based on this technology that targets an immune response binding HIV envelope protein to monoclonal antibodies specifically targeting CD40 receptors on the surface of dendritic cells. Once injected, the Env protein is thus delivered directly to the dendritic cells that play a key role in the education and activation of the immune system. 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.
HIV Monoclonal Antibody - Experimental
The peer-review journal Nature published a study on June 1, 2022, 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 HIV's entry into human CD4+ cells, the virus cannot replicate, and the HIV transmission process may be prevented.
HIV Treatment 2023
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 pre-exposure prophylaxis to reduce the risk of sexually acquired HIV on December 20, 2021.
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 is not adequately controlled by their current treatment regimen. 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 living 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: "A 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 Infection." This trial is sponsored by the NIAID/NIH. It was developed to provide a convenient delivery method compared to the IV route so patients can self-administer the medication.
HIV Tests March 2023
The WHO recommends HIV self-testing as an important approach to address gaps in HIV diagnoses The USPSTF recommends screening for HIV infection in adolescents and adults who are at increased risk of infection. HIV tests can be ordered online at Ulta Lab Tests.
HIV and COVID-19 Vaccination
The International Journal of Infectious Disease 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 compared with healthy individuals. Additional strategies, such as a booster vaccination with mRNA COVID-19 vaccines, might improve seroprotection for these patients.
HIV and Mpox Infections
The U.S. White House National Mpox Response noted that data in 2023 suggests approximately 38–50% of people diagnosed with mpox also have HIV.
The Lancet published on February 21, 2023: Mpox in people with advanced HIV infection: a global case series. Severe complications were more common in people with a CD4 cell count of fewer than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotizing skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalized, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat, and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance.
Sexually Transmitted Disease Vaccines
The sexually transmitted disease vaccine summary was updated in March 2023.
HIV Vaccine News For 2023
January 23, 2023 - The end of the Mosaico HIV vaccine trial must lead to a continued drive to innovate as well as an urgency to ensure that proven HIV prevention and treatment options reach all who need them, says UNAIDS.
January 18, 2023 - The Janssen Pharmaceutical Companies of Johnson & Johnson, together with a consortium of global partners, announced the results of an independent, scheduled data review of the Phase 3 Mosaico study of Janssen's investigational HIV vaccine regimen. The study's independent Data and Safety Monitoring Board determined that the regimen was not effective in preventing HIV infection compared to placebo. Therefore, the Mosaico clinical trial will be discontinued.
January 8, 2023 - The Conversation published an article: HIV remains a leading killer in Africa despite medical breakthroughs.
December 22, 2022 - Daniel O'Day, Chairman, and CEO of Gilead Sciences, commented, "Gilead scientists have developed a unique and potent antiretroviral medicine in Sunlenca with the potential for flexible dosing options. Our goal is to deliver multiple long-acting options for treatment and prevention that are tailored to the needs of people living with HIV and people who could benefit from PrEP medicines."
December 14, 2022 - GW Researchers' new techniques of cell sampling and a stepwise approach to immune system stimulation could open new avenues for HIV vaccine design.
December 13, 2022 - The U.S. NIH published an article: Progress toward an eventual HIV vaccine.
December 2, 2022 - Researchers Leggat et al. reported results of a phase 1 clinical trial showing that a germline-targeting priming immunogen (eOD-GT8 60mer) was safe and feasible and induced targeted bnAb-precursor responses in 97% of vaccine recipients at substantial frequencies in each individual. bnAb-precursor responses made favorable gains in mutation and affinity after booster vaccination. The results establish proof of principle for this reductionist vaccine approach and encourage the development of additional boosters to induce bnAbs.
December 1, 2022 - The NEJM published a Perspective: It Ain't Over Till It's Over…but It's Never Over — Emerging and Reemerging Infectious Diseases.
November 2, 2022 - "We are excited to have published the data on this important clinical study in such a prestigious journal, reaching a wide readership. Our T-cell vaccine approach has the potential to play a critical role in strategies to cure HIV infection. AELIX is a leader in developing vaccine-based solutions for HIV cure," said Dr. Christian Brander, co-founder, and chief scientific officer at AELIX and principal investigator at IrsiCaixa, in a press release.
October 25, 2022 - The U.S. NIH reported: An experimental HIV vaccine, delivered in increasing doses over several days, led to long-lasting and diverse antibody production in monkeys. The study's findings suggest that a long-prime, slow-delivery (12 days) immunization approach holds promise for difficult vaccine targets and suggests value for tuning germinal centers to maximize antibody responses.
October 25, 2022 - ViiV Healthcare announced positive findings from its phase IIa proof-of-concept study of N6LS, a novel, investigational, broadly neutralizing antibody that is being studied at two dosing levels in adults living with HIV. The study showed that a single infusion of N6LS demonstrated strong antiviral efficacy at both doses while also being well-tolerated by study participants.
October 20, 2022 - The U.S. NIH confirmed a three-dose course of the hepatitis B vaccine HEPLISAV-B fully protected adults living with HIV who had never been vaccinated against or infected with the hepatitis B virus (HBV), according to the ongoing Phase 3 ACTG A5379 clinical study.
October 20, 2022 - Advanced BioScience Laboratories announced it was awarded a contract for "Preclinical and translational vaccine development for HIV and other candidate agents" by the Division of AIDS within the National Institute of Allergy and Infectious Disease of the U.S. NIH.
October 11, 2022 - The Lancet HIV published an extensive study on the future of TB vaccine development. New tuberculosis vaccine candidates that are in the development pipeline need to be studied in people with HIV, who are at high risk of acquiring Mycobacterium tuberculosis infection and tuberculosis disease and tend to develop less robust vaccine-induced immune responses.
October 3, 2022 - Studies from Scripps Research and collaborators combine bioinformatics and other techniques to develop new vaccine candidates against HIV. The research describes the first steps in a vaccine approach that aims to prompt the creation of broadly neutralizing antibodies (bnAbs)—antibodies that are broad enough to fight and protect against many different variants of a virus.
September 29, 2022 - The peer-review journal Cell published - Study #1: Human immunoglobulin repertoire analysis guides the design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Study #2: Membrane-bound mRNA immunogens lower the threshold to activate HIV Env V2 apex-directed broadly neutralizing B cell precursors in humanized mice.
September 20, 2022 - Merck confirmed it would initiate a new Phase 3 clinical program with once-daily islatravir for the treatment of people with HIV-1 infection. These new Phase 3 studies will evaluate a once-daily oral combination of doravirine 100 mg and a lower dose of islatravir (DOR/ISL). One study will evaluate DOR/ISL in previously untreated adults with HIV-1 infection, and two studies will evaluate DOR/ISL as a switch in antiretroviral therapy in adults with HIV-1 infection who are virologically suppressed.
September 16, 2022 - "Dosing the first participant with EBT-101 is a landmark event that solidifies Excision's position as a pioneer in gene editing," said Daniel Dornbusch, CEO of Excision. EBT-101 achieved robust CRISPR-based editing of HIV proviral DNA without detectable off-target effects.
September 7, 2022 - The peer-review journal Science Translational Medicine published a study: Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection. CH505 viral isolates were isolated that mutated the V1 to escape both the infection-induced and vaccine-induced antibodies. These results define the specificities of a vaccine-induced nAb response and the protective titers of HIV-1 vaccine-induced nAbs required to protect nonhuman primates from low-dose mucosal challenge by SHIVs bearing a primary transmitted/founder Env.
August 29, 2022 - The journal Nature published: Leveraging lessons learned from the COVID-19 pandemic for HIV. 'We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.'
August 22, 2022 - Gilead Sciences, Inc. announced that the European Commission granted Marketing Authorization for Sunlenca® (lenacapavir) injection and tablets for the treatment of HIV infection, in combination with other antiretrovirals, in adults with multi-drug resistant HIV infection for whom it is otherwise not possible to construct a suppressive anti-viral regimen.
July 12, 2022 - The JAMA journal published: Dual Anti-HIV Antibodies Provide Long-term Viral Suppression. 'The antibody combination was ineffective in patients with HIV that was resistant to 1 or both antibodies. However, future antibodies with greater potency and durability, possibly supplemented with injectable long-term antiretroviral drugs, "could lead to ART-free HIV suppression for extended periods (years)," the authors wrote.'
July 8, 2022 - A new preclinical study led by Oregon Health & Science University researcher Jonah Sacha, Ph.D. will evaluate an experimental drug's (leronlimab) potential use as a gene therapy that could prevent people who have HIV from having to take daily antiviral drugs.
June 7, 2022 - Emory University in Atlanta, GA, confirmed it is participating in a clinical trial to test mRNA-based HIV vaccine candidates in humans.
July 4, 2022 - NJP Vaccines published - Viral vectors have been around for over forty years, and many of them have been used and are currently being used as vaccines against infectious diseases.
June 20, 2022 - The Fred Hutch Center in Washington published an article: Optimizing antigen design may improve HIV vaccine efforts.
June 7, 2022 - The JAMA published an Original Investigation: Analysis of Postvaccination Breakthrough COVID-19 Infections Among Adults With HIV in the United States. In this cohort study of 113 994 patients, the risk of breakthrough infection was low overall (3.8%) but 28% higher in people with vs. without HIV.
June 3, 2022 - HOOKIPA Pharma Inc. announced preclinical data, in collaboration with Gilead Sciences, Inc., on arenaviral therapeutic vaccines that are being studied as a component of a potential functional curative regimen for HIV.
May 11, 2022 - The Coalition for Epidemic Preparedness Innovations (CEPI) and the Kenya-based Victoria Biomedical Research Institute announced a new clinical research program that aims to evaluate the safety and immunogenicity of homologous and heterologous COVID-19 vaccine booster regimens in adolescents and adults living with HIV. CEPI will provide up to US$12.5 million to assess this "mix and match" booster approach.
May 4, 2022 - The peer-review journal Science Advances published a Research Article: Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that bind the C1C2 gp120 domain. 'Our findings support using these immunogens to activate VRC01 B cells in humans.'
December 20, 2021 - The U.S. FDA approved Apretude (cabotegravir extended-release injectable suspension) for certain at-risk adults and adolescents.