This phase 1 study will evaluate the safety, tolerability, and immune responses of two experimental mRNA HIV vaccines in adults living with HIV who are in overall good health. The study will enroll about 42 participants at multiple study sites. Researchers will assess whether these vaccines can start or strengthen antibody responses against HIV. The study will also evaluate how a closely monitored planned pause in antiretroviral therapy affects these immune responses.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
42
Intramuscular injection
Intramuscular injection
Alabama CRS (Site ID: 31788)
Birmingham, Alabama, United States
RECRUITINGThe Ponce de Leon Center CRS (Site ID: 5802)
Atlanta, Georgia, United States
RECRUITINGThe Hope Clinic of the Emory Vaccine Center CRS (Site #: 31440)
Decatur, Georgia, United States
NOT_YET_RECRUITINGBeth Israel Deaconess Medical Center / BIDMC VCRS (Site ID: 32077)
Boston, Massachusetts, United States
RECRUITINGColumbia P&S CRS (Site#: 30329)
New York, New York, United States
NOT_YET_RECRUITINGUniversity of Rochester Vaccines to Prevent HIV Infection CRS (Site#: 31467)
Rochester, New York, United States
NOT_YET_RECRUITINGPenn Prevention CRS (Site#: 30310)
Philadelphia, Pennsylvania, United States
NOT_YET_RECRUITINGHouston Advancing Research Team CRS (Site # 31473)
Houston, Texas, United States
NOT_YET_RECRUITINGSeattle Vaccine and Prevention CRS (Site ID: 30331)
Seattle, Washington, United States
RECRUITINGFundacion Huesped CRS (Site ID: 31957)
Buenos Aires, Buenos Aires, Argentina
NOT_YET_RECRUITING...and 6 more locations
Local reactogenicity following study product administration
Incidence and severity of solicited local reactogenicity signs and symptoms (injection site pain, erythema, and swelling), graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
Time frame: 14 days following each vaccination
Systemic reactogenicity following study product administration
Incidence and severity of solicited systemic reactogenicity signs and symptoms (fever, fatigue, myalgia, arthralgia, headache, chills, nausea), graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
Time frame: 14 days following each vaccination
Number and description of serious adverse events (SAEs)
Time frame: Through study completion, expected to be up to 88 weeks
Number and description of medically attended adverse events (MAAEs)
Time frame: Through study completion, expected to be up to 88 weeks
Number and description of adverse events of special interest (AESIs)
Time frame: Through study completion, expected to be up to 88 weeks
Number and description of adverse events leading to study product discontinuation or participant withdrawal
Time frame: Through study completion, expected to be up to 88 weeks
Number and description of adverse events (AEs) following study product administration
Time frame: 30 days following each vaccination
Response rate of differential serum neutralizing antibody responses to precursor detection viruses
Proportion of participants with serum antibody responses demonstrating differential neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses
Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Response rate of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart
Proportion of participants with serum antibody responses demonstrating differential neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart
Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Frequency of Env-specific and V3-glycan-specific B cells
Frequency of total Env-specific and V3-glycan-specific B cells, as assessed by flow cytometry
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences
Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences, as assessed by B-cell sorting and BCR sequencing
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Frequency of Env-specific and V3-glycan-specific B cells after last vaccination and after ART restart
Frequency of total Env-specific and V3-glycan-specific B cells, as assessed by flow cytometry
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences after last vaccination and after ART restart
Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences, as assessed by B-cell sorting and BCR sequencing
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers
Proportion of participants with serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers
Magnitude of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers
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Epitope specificity of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Response rate of neutralization activity against heterologous tier 2 viruses
Proportion of participants with neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of neutralization activity against heterologous tier 2 viruses
Magnitude of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Breadth of neutralization activity against heterologous tier 2 viruses
Breadth of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay
Time frame: At Baseline (Week 0) and 2 weeks after last vaccination
Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart
Proportion of participants with serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart
Magnitude of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart
Epitope specificity of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Response rate of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart
Proportion of participants with neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart
Magnitude of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Breadth of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart
Breadth of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay
Time frame: 6 weeks after last vaccination and 8 weeks after ART restart
Change in HIV Env sequence characteristics during ATI
Comparison of HIV envelope (Env) sequence evolution during analytic treatment interruption (ATI) between participants who develop V3-glycan-specific antibodies and those who do not
Time frame: During ATI
Change in HIV gag sequence characteristics during ATI
Comparison of HIV gag sequence evolution during analytic treatment interruption (ATI) between participants who develop V3-glycan-specific antibodies and those who do not
Time frame: During ATI