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A Trial Is Underway That Could Be 'the Last Roll Of The Dice' For An HIV Vaccine This Decade

CNN  — 

A novel trial that has been described as "the last roll of the dice" for a generation of HIV vaccines has entered its latter stages.

Called PrEPVacc, the trial is testing two vaccines alongside two forms of pre-exposure prophylaxis (PrEP) to test vaccine efficacy while offering protection to prevent the spread of HIV.

African-led and coordinated out of Entebbe, Uganda, with international support, its success could mark the start of a new phase of vaccine development. Should it fail, it could also see immunologists give up on a generation of vaccines.

Nearly 40 years since HIV was identified as the cause of AIDS, and 36 years since the first HIV vaccine trial, the medical community still does not have a working vaccine. Although antiretroviral treatments are well established, access varies. UNAIDS estimates 630,000 people died from AIDS-related illness globally in 2022, while 39 million people are living with HIV, including 1.3 million people newly infected last year.

The hope is that PrEPVacc will succeed where other trials have fallen short – most recently HVTN 702 (dubbed "Uhambo"), halted in February 2020, HVTN 705 ("Imbokodo"), discontinued in 2021 and HVTN 706 ("Mosaico") in 2023, all of which were found to be safe but ineffective at preventing HIV.

Only one clinical trial, which took place in Thailand with results published in 2009, has been found to show modest effectiveness at preventing HIV infection. The efficacy of that vaccine, RV144, was about 30% (although the findings continue to be debated). For PrEPVacc to be considered a success, either of the two vaccines being tested will need to achieve an efficacy of at least 70%.

One vaccine combines pieces of synthetic HIV DNA with a protein base, while the other combines DNA, MVA (a weakened pox virus) and a protein base, like that used in RV144.

"This is an evolution (of RV144), not a revolution," said Jonathan Weber, lead applicant and coordinator of PrEPVacc, and director of the Imperial College Academic Health Science Centre in London. "These are both regimens which have never gone into efficacy study before," he added, describing the vaccines as "the best we feel, at the moment, that medical science can provide."

The clinical trial began enrollment December 2020 and signed up the last of its 1,513 participants in March 2023. The participants are all between 18-40 years old and live in South Africa, Uganda or Tanzania.

All three countries have high rates of HIV/AIDS in adults, sitting within the top 15 countries in the world per 2021 estimates. But that is not necessarily why they were chosen to participate, said Eugene Ruzagira, PrEPVacc trial director.

Ruzagira is himself Ugandan, based in Entebbe at the Medical Research Council/Uganda Virus Research Institute, and oversees a team of researchers at trial sites in Durban, South Africa, Masaka, Uganda, and Dar es Salam and Mbeya, Tanzania. These locations, he explained, "had experience doing HIV prevention studies, not only vaccine trials, have established very good connections with the communities, and have the infrastructure we require."

Though funding for PrEPVacc came from the European Union-sponsored EDCTP, "this genuinely needed to be an African study led by Africans and coordinated in Africa, where the data is analyzed in Africa and the laboratory work is done in Africa," said Weber.

"It's about time," Ruzagira said. "We've had a few decades of preparation."

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In the randomized trial, each participant receives four injections of either vaccine A or B or a saline placebo over a 48-week schedule, along with a course of PrEP taken daily until week 26, a fortnight after the third injection – the logic being that the immune response will peak around then, said Ruzagira.

The US Centers for Disease Control and Prevention estimates PrEP taken as prescribed reduces the risk of getting HIV from sex by about 99%, and among people injecting drugs by at least 74%. The PrEPVacc trial is distributing two forms of PrEP pills, Truvada or Descovy, and is testing if the newer Descovy has the same or better effectiveness among the trial cohort. (Descovy currently holds FDA approval for use by men but not women.) Evaluating the combination of a trial HIV vaccine and PrEP is a first, say organizers.

Luwano Geofrey was the first trial participant in Masaka, Uganda. "I felt this was a big project that needed our support as a community," he told CNN, in an interview conducted in the Luganda language by a PrEPVacc community engagement officer.

"One of the things I liked most was that participants would have routine HIV counseling and testing, free condoms, PrEP and support and care," he explained. "I live and work in (a) fishing community. Most times, we lack these services."

PrEP has not achieved high usage levels in Africa, said Weber, describing "massive issues about access and uptake (and) acceptance of PrEP as a reasonable intervention."

Social stigma can complicate matters. In Uganda, for instance, PrEP is still distributed by HIV clinics, said Ruzagira, and being seen to enter a well-known HIV clinic can put people off seeking the medication.

"What we always hoped was once people started PrEP, they would see that it was easy, it was tolerable, it was acceptable, and would continue using it as long as they were at risk," said Weber.

After 26 weeks, trial participants are given the option to access PrEP from public health facilities, but not everyone is transitioning to long-term use, say organizers.

Geofrey said his PrEP use during the 26 weeks was not always consistent, and that afterward, he tried to secure the drug from a local facility, but "more often than not (it) ran out of stock."

Such issues are not limited to Uganda. "I would say that PrEP uptake is not what we would like it to be," said Nishanta Singh, principal investigator at the Verulam clinical research site in Durban, South Africa.

"But it's something that the community and the general population is starting to learn about," she added. "We are seeing an increase in PrEP uptake as the weeks of the trial go by. Obviously, it's not optimal, but it's a work in progress."

In Verulam, more than half of participants have already received all four injections. As with the other trial sites, participants are tested and receive counselling every four to eight weeks, and will be monitored until October 2024.

The trial team is blind to the data, which is processed by an Independent Data Monitoring Committee. The results of the trial are scheduled for release in the fourth quarter of 2024.

In the case of vaccine trials, no news can be good news. Trials can be halted by monitoring committees if early data indicates a lack of efficacy (as was the case with HVTN 702) but that has not yet been the case for PrEPVacc.

"This is indeed a good sign, however, it is possible that there have been very few infection events in this trial, given that PrEP use was also encouraged in all participants," said Sharon Lewin, a professor of medicine at The University of Melbourne.

Lewin, also president of the International AIDS Society, is not associated with the PrEPVacc trial, and offered caution regarding the vaccines' potential efficacy.

"I would predict that the DNA, MVA and protein vaccines won't provide too much protection from HIV infection, based on what we know from prior studies," she said, although she commended the integration of PrEP into the Africa-led study, noting, "it's also fantastic to see the first Phase 3 vaccine trial funded from outside the US."

Should one or both vaccines prove effective, further trials would be needed and would likely involve multiple international partners. Should it fall short, "it's really back to basics," said Weber. "There's nothing else around which looks any better of this generation of vaccine products."

"In this decade, it will be the last roll of the dice," he added. "My prediction is there won't be another efficacy study of an HIV vaccine until the 2030s."

Lewin does not believe that will be the case, pointing to new and rapidly advancing science.

One approach undergoing early testing is germline targeting, in which a series of slightly different vaccines are administered, designed to stimulate B-cells into producing "broadly neutralizing antibodies." These powerful but hard-to-elicit antibodies could potentially damage the HIV virus as it mutates in an attempt to escape them, scientists theorize.

And last summer, a Phase 1 trial began in the US and another in Rwanda and South Africa of multiple vaccines utilizing mRNA (messenger ribonucleic acid). MRNA instructs the body to create proteins which induce an immune response and has already been used successfully in two Covid-19 vaccines.

But for the PrEPVacc team and its participants, there's no option but to hold tight until the end of 2024 and hope that the results will be better than for other trials. "I did my very first HIV vaccine trial in 1991," recalled Weber. "I think that probably tells you all you need to know about the agony of the search."

Geofrey recalled what the trial asked of him: being told he and his wife should not bear children during its run; her initial concern that the PrEP bottles he came home with meant he was being treated for HIV; the initial disinformation in his community that the study was introducing HIV to participants, rather than seeking to prevent it. "It takes a lot of courage and time to be part of a trial like this," he reflected.

"I know if the vaccines being tested give us positive results, I will consider myself, other participants, and scientists as the heroes of this century."

Biostax Corp. Signs Collaboration Agreement With Immgenuity, Inc. To Pursue Remission In HIV

Orlando, FL, Aug. 29, 2023 (GLOBE NEWSWIRE) -- Immune Therapeutics, Inc. D/b/a Biostax Corp. (OTC Pink: IMUN) ("Biostax"), a hub-and-spoke biotech development engine, announces the signing of a research collaboration agreement with Immgenuity, Inc. The joint research will focus on using Immgenuity's IMTV014 and Biostax's Lodonal™ and JKB-122 both independently and together to determine if the immune modulatory effects of Biostax's drug therapies combined with Immgenuity's IMTV014 can achieve remission with HIV patients.

Under the terms of the agreement, Immgenuity and Biostax will collaborate to advance the development of novel immunotherapies for the treatment of HIV and other diseases. The collaboration will leverage Immgenuity's expertise in developing cutting-edge technologies for the identification and characterization of immune cell populations, mechanisms of immune escape, and Biostax's deep knowledge and experience in using naltrexone as an immune enhancing and anti-inflammatory agent.

Immgenuity's IMTVO14 vaccine platform is an immunotherapy, comprising a genetically modified HIV virus which is unable to block immune signaling like the natural HIV does. By restoring immune signaling, IMTVOI4 is expected to restore a normal, viable, and robust immune response to HIV and likely lead to clearing the virus even from the sanctuary areas where the virus persists despite aggressive anti-HIV drug treatment.

"While HIV treatment has advanced dramatically over the past three decades, people living with HIV still face a lifetime of therapy and chronic illness," said Sateesh Apte, MD. "Remission in HIV remains the ultimate aspiration for both Biostax's and Immgenuity's research and development efforts."

"Patients are required to be off all anti-viral medications before Immgenuity's vaccine platform can be administered and we expect Biostax's naltrexone-based drug candidates to work synergistically during the period when patients stop taking their anti-viral medications and before the vaccine's immune response takes effect, " said Dr. Apte. "This, along with Biostax's immune-modulating therapy and our other partnerships and internal programs, reflects our commitment to finding a therapy that will achieve remission for HIV and bring about an end to the HIV epidemic."

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"Based upon existing HIV data surrounding both JKB-122 and Lodonal™ we believe that by performing combined research we will generate additional compelling data, that complements our existing clinical data," said Noreen Griffin, Biostax's CEO. "We are delighted to enter into this partnership that will further develop our product candidates for the treatment of patients with HIV."

Clinical Program JKB-122 and Lodonal

Biostax will also look to fast track a Phase 2b trial with the FDA: "Effects of JKB-122 and Lodonal™ on T-Cell Immune Activation and Inflammation in Non-Responders or who are Failing their CAR-T therapy with HIV." The primary end point is to show a decrease in comorbidities and opportunistic infection and clinical symptoms such as diarrhea, fatigue, pain, upper respiratory infections, skin disorders, and confirm changes of T-cell immune activation and reduction inflammation biomarkers.

Prior clinical trials have shown Lodonal™ and JKB-122 can modulate the immune system by increasing NK cells, CD4, improve the CD4/CD8 and reduce opportunistic infection and pain in HIV patients while reducing inflammation. The success in these trials will provide evidence for the use of Lodonal™ and/or JKB-122 as part of combined therapy for remission and immune restoration in HIV patients.

About Lodonal and JKB-122

Biostax has developed a rapid release oral formulation of the drug substance "low dose naltrexone", known as Lodonal™, for use as an active immunotherapy drug with anti-inflammatory properties. Lodonal™ is one of the first drugs approved to be taken once-a-day as an immune system regulator for the management of HIV/AIDS. The approval by NAFDAC was based on the results of a bridging trial that resulted in a 44% increase in CD4 Count versus an 11% increase for standard of care patients.

Unlike "single target" immune suppressors, or drugs that require a specific cell receptor to act, Lodonal™ and JKB-122's molecular structure allows it to be a promiscuous antagonist of various classes of receptors/proteins (multiple targets), eliciting multiple complimentary effects. Beyond modulation of the cell cycle by way of growth factor-like activities downstream of opioid receptors, clinical trials indicated that it reduces the overall activation state (metabolic shift) of cells responsive to pathogen signals, damage signals, or both (drivers of inflammation).

Our recent research shows that Lodonal™ and JKB-122's molecular shape allows it to bind to a variety of cellular receptors and proteins beyond the surface and nuclear opioid receptors. Because noroxymorphone at low dose can bind surface receptors as well as diffuse rapidly into the cell and its nucleus, several parallel mechanisms of action combine.

About Biostax

Biostax is an innovative biopharmaceutical company that acquires and develops immune restoration pharmaceutical and medical technology (MedTech) products with a well -defined path to market. We use a hub-and-spoke business model, where the parent company (hub) holds a centralized management and administrative team, and each subsidiary (spoke) operates a specialized development team focused on individual product pipelines.

Where Biostax has a diversity of product pipelines that will provide revenue while reducing risk, our goal is to develop new therapies that provide disease remission by restoring immune balance for patients with autoimmune, inflammatory, and infectious diseases without suppressing their immune system. Restoring homeostasis or balance to the immune system is the first step to a cure by improving patients' lives in chronic illness caused by immune dysfunction and inflammation. Www.Biostaxcorp.Com

About Immgenuity, Inc.

Immgenuity, Inc. Is a biotechnology company dedicated to developing innovative immunotherapy solutions to improve the lives of patients suffering from HIV. The company's lead product candidate is IMTV014, a novel immunotherapy for HIV and NeuroAIDS, which has shown to be safe in preclinical studies. Immgenuity, Inc. Is headquartered in Dover, Delaware and is led by a team of experienced biotech professionals with deep expertise in infectious diseases, immunology, virology, and drug development. For more information, visit https://immgenuity.Com

Forward Looking Statement

This press release may contain information about our views of future expectations, plans and prospects that constitute forward-looking statements. All forward-looking statements are based on management's beliefs, assumptions, and expectations of Immune's future economic performance, considering the information currently available to it. These statements are not statements of historical fact. Although Immune believes the expectations reflected in such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Immune does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law. No assurances can be made that Immune will successfully acquire its acquisition targets. Forward-looking statements are subject to a number of factors, risks, and uncertainties, some of which are not currently known to us, that may cause Immune's actual results, performance, or financial condition to be materially different from the expectations of future results, performance, or financial position. Actual results may differ materially from the expectations discussed in forward-looking statements. Factors that could cause actual results to differ materially from expectations include general industry considerations, regulatory review and approval of our prospective products, changes in local or national economic conditions and other risks set forth in "Risk Factors" included in our filings with the Securities and Exchange Commission.

Disclaimer

The information provided in this press release is intended for general knowledge only and is not a substitute for professional medical advice or treatment for specific medical conditions. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition. This information is not intended to diagnose, treat, cure, or prevent any disease.

Biostax Contact:

Noreen M. Griffin

Chief Executive Officer

ir@biostax.Net

1-888-391-9355

Absci And Caltech Receive Grant From Bill And Melinda Gates Foundation For HIV Vaccine Effort

The grant will support the joint effort of both establishments to discover affordable HIV therapeutic vaccinations, with the goal of making a significant step forward in the fight against the global HIV and AIDS epidemic. 

The collaboration between Caltech and Absci, led by Dr. Pamela Bjorkman, brings together research capabilities and advanced technological expertise in structural biology and immunology, protein design, synthetic biology, and generative AI.

The teams will work to develop a novel HIV therapy that first exposes and then binds to a highly conserved epitope binding site on HIV-1 to potentially both treat and protect against infection from all strains of the virus. 

More than 40 years after the AIDS pandemic began, there is no vaccine or cure for HIV.

Antiretroviral therapies (ARTs) help many people live longer, healthier lives, but they do not completely eliminate the virus and must be taken for life. Additionally, the cost and inaccessibility of these drugs disproportionately affect millions of people from low-income and marginalized communities.

This new partnership between Caltech and Absci, facilitated by the grant from the Gates Foundation, aims to address this disparity by focusing on the affordability, scalability, and accessibility of HIV therapeutic vaccinations.

Dr. Stephen Mayo, Caltech professor and project co-leader, said: "We are thrilled to receive this grant from the Bill & Melinda Gates Foundation. We're committed to making transformative contributions to society through research and innovation, and we are excited to partner with Absci, who has developed a powerful de novo AI antibody platform that is helping to unlock new therapeutic possibilities."

"This collaboration with Absci allows us to combine our expertise and work towards a common goal of developing affordable HIV therapeutic vaccinations that can save lives and bring hope to millions." 

Sean McClain, CEO and founder of Absci, added: "We are honored to be partnering with Caltech on this critical project. At Absci, we are driven to transform lives through the power of generative AI and synthetic biology."

"By joining forces with Dr. Pamela Bjorkman and Dr. Stephen Mayo, and with support from the Gates Foundation, we believe we can make significant strides towards developing affordable HIV therapeutic vaccinations and positively impacting global health." 

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