mRNA Vaccines for HIV Prevention

Recruiting at 5 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Glucocorticoids, Immunoglobulin, Antiseizure, others

Disqualifiers: Pregnancy, Diabetes, Immunodeficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new mRNA vaccines designed to prevent HIV by teaching the body to produce specific antibodies, which fight viruses. Researchers aim to determine if these vaccines are safe and can effectively prompt the immune system to produce these protective antibodies. Prospective participants should be in good health, not living with HIV, and willing to attend regular clinic visits. They should also not have severe asthma or a history of serious reactions to vaccines. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications that might impair your immune response, like certain steroids, you may need to discuss this with the trial team. It's best to consult with the trial staff about your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that mRNA vaccines, like the ones being tested here, have been safely used in many people. These vaccines teach the body to fight specific viruses. In other studies with different mRNA vaccines, most people experienced only mild side effects, such as a sore arm, fatigue, or headache.

For these specific vaccines, called CH505M5 N197D mRNA-gp160 and CH505 TF mRNA-gp160, limited information exists about side effects. However, this study is in the early stages, focusing primarily on ensuring the treatment's safety. This is common in early trials, where researchers closely monitor for any side effects.

Overall, mRNA vaccines have been well-tolerated, but since this is a new treatment, monitoring reactions remains important. Prospective participants will receive detailed information from the study team about what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the mRNA vaccines for HIV prevention because they offer a novel approach compared to traditional HIV treatments, which mainly consist of antiretroviral therapies. Unlike these standard treatments that manage the virus, the mRNA vaccines aim to prevent HIV infection altogether. They work by using mRNA technology to instruct the body to produce proteins that trigger an immune response against the virus, potentially offering a proactive method against HIV. This approach could revolutionize HIV prevention by providing a way to prime the immune system before exposure, reducing the risk of infection.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

Research has shown that mRNA vaccines like CH505M5 N197D mRNA-gp160 and CH505 TF mRNA-gp160, studied in this trial, could help prevent HIV. These vaccines teach the immune system to produce special antibodies that block the virus from infecting cells. Early studies on similar mRNA vaccines indicate they are generally safe and can effectively strengthen the immune response. Although these specific vaccines are new, they use mRNA technology that has succeeded in other vaccines. Initial results suggest these vaccines could be an important step in preventing HIV. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults in good health who do not have HIV. It's designed to test the safety and potential of two new mRNA-based vaccines that aim to prepare the immune system against HIV.

Inclusion Criteria

Agrees to specific requirements for HIV prevention and counseling

Agrees to contraception and pregnancy testing requirements

My blood counts, liver, kidney functions, calcium levels, and blood pressure are within required ranges.

Exclusion Criteria

Breastfeeding/chestfeeding or pregnant

I have recently received blood products or immunoglobulin.

I have recently been vaccinated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CH505M5 N197D mRNA-gp160 at weeks 0, 8, and 16, followed by CH505 TF mRNA-gp160 at week 24

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CH505M5 N197D mRNA-gp160
• CH505 TF mRNA-gp160

Trial Overview The study involves two experimental vaccines, CH505M5 N197D mRNA-gp160 and CH505 TF mRNA-gp160, which are given in stages to see if they can stimulate the body's immune cells to fight HIV more effectively.

How Is the Trial Designed?

Group I: Group 4 (150 mcg) Experimental Treatment 2 Interventions

150 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 150 mcg CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Group II: Group 3 (100 mcg) Experimental Treatment 2 Interventions

100 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 100 mcg of CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Group III: Group 2 (50 mcg) Experimental Treatment 2 Interventions

50 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 50 mcg of CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Group IV: Group 1 (25 mcg) Experimental Treatment 2 Interventions

25 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 25 mcg of CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

CH505M5 N197D mRNA-gp160 is already approved in United States for the following indications:

Approved in United States as CH505M5 N197D mRNA-gp160 for:

• HIV Infections

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

A novel HIV therapeutic vaccine using unmodified and modified mRNA showed promise in enhancing HIV-specific T-cell responses when combined with immunomodulators like Vesatolimod and Nivolumab, indicating a potential strategy for achieving a functional cure.

In vitro assays demonstrated that this combination therapy not only boosted T-cell responses but also increased the secretion of key mediators (IFNγ, IP10, MIP-1α, and MIP-1β) that are crucial for controlling the virus, suggesting a robust immune response against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses. Usero, L., Leal, L., Gómez, CE., et al.[2023]

Nucleoside-modified mRNA-lipid nanoparticle vaccines targeting the HIV-1 envelope showed promising immune responses, generating high levels of gp120-specific antibodies in rabbits and rhesus macaques, indicating potential for effective vaccination.

While some non-human primates developed antibodies that could neutralize a tier 2 HIV strain, the overall neutralization breadth and durability of the antibodies were limited, suggesting that further optimization of the vaccine design and protocols is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques. Pardi, N., LaBranche, CC., Ferrari, G., et al.[2022]

The study evaluated the safety and immune response of the rgp160 HIV-1 vaccine in 138 HIV-negative volunteers, finding it to be safe with no major adverse reactions reported.

The vaccine induced strong antibody responses, particularly at the highest dose of 1,280 micrograms, and generated T cell responses against both the vaccine strain and some heterologous HIV strains, suggesting potential for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of humoral and cell-mediated anti-human immunodeficiency virus (HIV) responses in HIV sero-negative volunteers by immunization with recombinant gp160. Kovacs, JA., Vasudevachari, MB., Easter, M., et al.[2018]

Despite the challenges faced in the past fifteen years of HIV vaccine trials, significant progress has been made in understanding how to design effective vaccines that elicit strong immune responses, particularly through the induction of CD8+ CTL responses.

Current promising HIV vaccine regimens are being evaluated in human trials, and recent successes in simian models provide hope that a safe and effective vaccine could soon be developed to help control the global HIV epidemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV vaccine development: lessons from the past and promise for the future. Spearman, P.[2019]

Recent studies indicate that lower doses of broad neutralizing antibodies may effectively prevent HIV-1 infection, suggesting a new approach to vaccine development.

The RV144 trial demonstrated a 31% efficacy for an HIV-1 vaccine, providing optimism for future vaccine strategies, but further research is needed to enhance immunogens and understand how to better induce protective antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is developing an HIV-1 vaccine possible? Haynes, BF., Liao, HX., Tomaras, GD.[2021]

The recombinant gp160 vaccine was found to be safe and well tolerated in a study involving 208 volunteers over 24 months, with no significant adverse effects reported.

Despite inducing immune responses, the vaccine did not show any clinical benefit in altering the progression of HIV infection, as there was no impact on CD4 cell counts or viral levels compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant gp160 as a therapeutic vaccine for HIV-infection: results of a large randomized, controlled trial. European Multinational IMMUNO AIDS Vaccine Study Group. Goebel, FD., Mannhalter, JW., Belshe, RB., et al.[2019]

Modified Newcastle disease virus (NDV) vectors expressing the SIV envelope protein gp160 were shown to be safe and effective in eliciting strong immune responses in guinea pigs, indicating their potential as a vaccine vector for HIV.

These NDV vectors not only induced SIV-specific humoral and mucosal immune responses but also effectively generated neutralizing antibodies against different strains of SIV, suggesting their promise in HIV vaccine development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified Newcastle Disease virus as an improved vaccine vector against Simian Immunodeficiency virus. Manoharan, VK., Khattar, SK., LaBranche, CC., et al.[2019]

The MN rgp160 vaccine was found to be safe for healthy, uninfected volunteers, with no serious adverse effects reported during the study.

The vaccine effectively induced a strong immune response, with 15 out of 20 participants developing neutralizing antibodies and significant T cell memory, particularly with the regimen that included a fourth dose of 800 micrograms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of immunologic responses to HIV-1MN recombinant gp160 vaccine by dose and schedule of administration. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. Gorse, GJ., McElrath, MJ., Matthews, TJ., et al.[2019]

An mRNA vaccine that co-expresses HIV-1 envelope and SIV Gag proteins successfully induced broad neutralizing antibodies and significantly reduced the risk of infection in rhesus macaques, demonstrating its potential as a protective vaccine against HIV.

The vaccination regimen, which included priming with a specific HIV-1 envelope followed by multiple boosters, resulted in a 79% reduction in infection risk during repeated challenges, indicating strong immunogenicity and effectiveness against prevalent HIV strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multiclade env-gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques. Zhang, P., Narayanan, E., Liu, Q., et al.[2023]

The recombinant gp160 vaccine was found to be safe in a study involving 60 low-risk, uninfected subjects, with no serious adverse effects reported.

The vaccine induced neutralizing antibodies against HIV-1 in a significant number of participants, particularly in those receiving the higher dose of 50 micrograms and after a booster dose, suggesting its potential efficacy in generating an immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a fully glycosylated recombinant gp160 human immunodeficiency virus type 1 vaccine in subjects at low risk of infection. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group Network. Belshe, RB., Clements, ML., Dolin, R., et al.[2019]

The new mRNA-based therapeutic vaccine, combining activation signals (TriMix) with HIV-specific antigens, effectively activated dendritic cells from HIV-infected individuals, leading to enhanced T-cell responses and cytokine production.

In mouse models, the vaccine not only increased antigen-specific cytotoxic T-lymphocyte responses but also showed that the addition of TriMix further boosted these immune responses, indicating its potential for developing effective therapeutic HIV vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix). Guardo, AC., Joe, PT., Miralles, L., et al.[2019]

Recent advancements in HIV-1 vaccine development have led to a better understanding of the virus's structure and function, resulting in innovative vaccine strategies that show promise in eliciting immune responses.

Several vaccine candidates are currently in clinical trials, with some demonstrating the ability to reduce disease severity in nonhuman primates, indicating potential effectiveness in humans, even if they do not completely prevent infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances and challenges in HIV-1 vaccines. Rodriguez-Chavez, IR., Allen, M., Hill, EL., et al.[2019]

The V-1 Immunitor HIV vaccine was well tolerated in a study of 40 patients, showing no significant adverse effects and resulting in a mean body weight gain of 2.2 kg over 27 weeks.

The vaccine led to significant increases in CD4 and CD8 cell counts, with increases of 51 (18%) and 172 (16%) cells/mm3 respectively, suggesting potential efficacy in enhancing immune response against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of an oral HIV vaccine (V-1 Immunitor) in AIDS patients at various stages of the disease. Jirathitikal, V., Bourinbaiar, AS.[2004]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06557785?term=AREA%5BFunderTypeSearch%5D(NIH)&rank=7

Study Details | NCT06557785 | A Clinical Trial to Evaluate ... This is a multicenter, open-label, non-randomized, dose escalation, first-in-human (FIH) trial to evaluate the safety and immunogenicity of CH505M5 N197D ...

2. ctv.veeva.com ctv.veeva.com/study/a-clinical-trial-to-evaluate-the-safety-and-immunogenicity-of-ch505m5-n197d-mrna-gp160-followed-by-c

A Clinical Trial to Evaluate the Safety and Immunogenicity of ... A Clinical Trial to Evaluate the Safety and Immunogenicity of CH505M5 N197D mRNA-gp160 Followed by CH505 TF mRNA-gp160 in Adults in Overall Good ...

3. infectiousdiseases.cuimc.columbia.edu infectiousdiseases.cuimc.columbia.edu/research/clinical-trials

Clinical Trials | Infectious Diseases - Columbia University This is a first-in-human phase 1 clinical trial where we will be testing 2 study vaccines, CH505M5 N197D mRNA-gp160 and CH505 TF mRNA-gp160. The goal is to ...

4. frontierspartnerships.org frontierspartnerships.org/journals/british-journal-of-biomedical-science/articles/10.3389/bjbs.2025.14557/full

A Systematic Review of Clinical Trials Using mRNA Vaccines ... Despite the lack of long-term data, this systematic review suggests that these mRNA vaccine candidates are safe and effective with the potential to shape the ...

5. rsc.niaid.nih.gov rsc.niaid.nih.gov/clinical-research-sites/ch505m5-n197d-mrna-gp160-ch505-tf-mrna-gp160-and-ch505-w24-mrna-gp160

CH505M5 N197D mRNA-gp160, CH505 TF ... CH505M5 N197D mRNA-gp160, CH505 TF mRNA-gp160 and CH505 w24 mRNA-gp160. Document Date. Monday, September 22, 2025. Contact Us · FAQs · Veeva Vault ...

6. trialx.com trialx.com/clinical-trials/listings/317923/a-clinical-trial-to-evaluate-the-safety-and-immunogenicity-of-ch505m5-n197d-mrna-gp160-followed-by-ch505-tf-mrna-gp160-in-adults-in-overall-good-health-without-hiv/?&radius=50

A Clinical Trial to Evaluate the Safety and Immunogenicity ... The primary hypotheses are: the CH505M5 N197D mRNA-gp160 will expand CH235-like B cell precursors,; the CH505 TF mRNA-gp160 will boost CH235- ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06557785/a-clinical-trial-to-evaluate-the-safety-and-immunogenicity-of-ch505m5-n197d-mrna-gp160-followed-by-ch505-tf-mrna-gp160-in-adults-in-overall-good-health-without-hiv

A Clinical Trial to Evaluate the Safety and Immunogenicity ... A Clinical Trial to Evaluate the Safety and Immunogenicity of CH505M5 N197D mRNA-gp160 Followed by CH505 TF mRNA-gp160 in Adults in Overall Good ...