Document text
Principal Investigator: Margaret Juliana McElrath
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2023
Award: $3,200,000
Funding agency: National Institute of Allergy and Infectious Diseases
Project Abstract
This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership
Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial, CoVPN 3008 (the Ubuntu
study) entitled “Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-
CoV-2 Variants of Concern.”
As the global COVID-19 pandemic has persisted, it has become clear not only that there are great risks faced
by people who are immunocompromised, but also that there is an urgent need to better understand infection and
disease in these populations so we can prevent severe COVID-19 as well as chronic SARS-CoV-2 infections
that could promote transmission and the emergence of new, dangerous variants. This is particularly true for the
over 37 million people living with HIV (PLWH) who are concentrated in sub-Saharan Africa and have been
significantly underrepresented in COVID-19 vaccine trials.
This novel study aims to address critical knowledge gaps by evaluating COVID-19 mRNA vaccine efficacy
among PLWH, including the influence of prior infection and degree of immunocompromise. This multicenter trial
comparing different regimens of the Moderna mRNA-1273 and mRNA-1273.222 vaccines will test the efficacy
of the vaccines in preventing COVID-19 disease regardless of severity, and in preventing COVID-19 severe
disease, in people who are at risk for symptomatic and severe COVID-19 in areas of the world where the
prevalence of SARS-CoV-2 Variants of Concern is substantial.
This is the first large scale study evaluating the effectiveness of mRNA vaccines against symptomatic and severe
COVID-19 among PLWH. In this study, at Month 0 (enrollment) all participants will receive a 100-mcg dose of
mRNA-1273. At Month 1, all participants without evidence of prior SARS-CoV-2 infection at baseline (based on
serology) will receive a second dose of mRNA-1273. At Month 6, all participants (regardless of baseline SARS-
CoV-2 status) will receive a 100-mcg dose of either mRNA-1273 or mRNA-1273.222, depending on their
randomization at enrollment. All trial endpoint assays will be done using qualified and validated assays for
diagnosis and immune monitoring.
The follow up of this study is divided into two stages: Pre-Month 6 stage (visits up to and including Month 6) and
post-Month 6 stage (visits through to Month 12). This allows a timely evaluation of the pre-Month 6 study
objectives as soon as Month 6 diagnostic data are available without the need to wait until the end of Month 12
follow up. Specific aims of this study pertaining to both pre- and post-Month 6 stages are to assess the relative
risk of symptomatic and severe COVID-19 after the first vaccine dose at Month 0 through to Month 6 in PLWH
who are SARS-CoV-2 negative at baseline who receive a 2-dose mRNA-1273 vaccine regimen vs. in PLWH
who are SARS-CoV-2 positive at baseline who receive a 1-dose mRNA-1273 regimen, as well as to assess this
relative risk for complete follow-up through to Month 12. Specific aims of this study pertaining to the post-Month
6 stage are to assess the relative risk of symptomatic and severe COVID-19 after the Month 6 dose through to
Month 12 among those who received mRNA-1273 at Month 6 vs. those who received mRNA-1273.222 at Month
6. Additionally, this study will assess safety and tolerability of mRNA-1273 and mRNA-1273.222 in PLWH and
adults who are at risk of severe COVID-19 in both the pre-Month 6 and post-Month 6 stages.
The study will also seek to characterize SARS-CoV-2 nucleic acid amplification test (NAAT) persistence, viral
shedding and the evolution of viral mutations among participants who acquire SARS-CoV-2 infection. By
collecting efficacy and safety data in over half-a-dozen countries across sub-Saharan Africa, the study team
hopes to inform regulators in the region and help facilitate access to mRNA vaccine technology across Africa.
Importantly, the study will also assess both cellular and antibody immune correlates of protection against
symptomatic COVID-19 and other outcomes.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Active Follow-up><Address><Adult><Adult Human><Africa><Africa South of the Sahara><Antibodies><Area><Assay><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 Prevention Network><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 negative><COVID-19 outbreak><COVID-19 pandemic><COVID-19 positive><COVID-19 positivity><COVID-19 prevention><COVID-19 public health crisis><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 negative><COVID19 outbreak><COVID19 pandemic><COVID19 positive><COVID19 positivity><COVID19 prevention><COVID19 public health crisis><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cellular Immune Function><Chronic><Clinical Trials><CoV-2><CoV2><CoVPN><Country><Dangerousness><Data><Diagnosis><Diagnostic><Disease><Disorder><Dose><End Point Assay><Endpoint Assays><Enrollment><Evaluation><Evolution><Genetic Alteration><Genetic Change><Genetic defect><HIV><Health><Human Immunodeficiency Viruses><Immune><Immune Monitoring><Immune response><Immunes><Immunity><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic Monitoring><Immunological Monitoring><Immunological response><Immunomonitoring><Immunosuppressed Host><Infection><Knowledge><LAV-HTLV-III><Laboratories><Lead><Leadership><Lymphadenopathy-Associated Virus><Moderna COVID-19 vaccine><Moderna coronavirus disease 2019 vaccine><Multi-center trial><Multicenter Trials><Mutation><Nucleic Acid Amplification Tests><Nucleic Acid Testing><Outcome><Participant><Pb element><Persons><Population><Prevalence><Qualifying><RNA vaccine><RNA-based vaccine><Randomized><Regimen><Relative Risks><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 negative><SARS-CoV-2 outbreak><SARS-CoV-2 pandemic><SARS-CoV-2 positive><SARS-CoV-2 positivity><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Serology><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 outbreak><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 positive><Severe acute respiratory syndrome coronavirus 2 positivity><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severities><Site><Sub-Saharan Africa><Subsaharan Africa><Technology><Transmission><Vaccination><Vaccines><Variant><Variation><Viral><Viral Shedding><Virus Shedding><Virus-HIV><Visit><Wuhan coronavirus><active followup><adulthood><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><assess effectiveness><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 negative><coronavirus disease 2019 outbreak><coronavirus disease 2019 pandemic><coronavirus disease 2019 positive><coronavirus disease 2019 positivity><coronavirus disease 2019 prevention><coronavirus disease 2019 prevention network><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 outbreak><coronavirus disease-19 pandemic><coronavirus disease-19 prevention><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><determine effectiveness><effectiveness assessment><effectiveness evaluation><efficacy study><efficacy testing><efficacy trial><enroll><evaluate effectiveness><examine effectiveness><follow up><follow-up><followed up><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><followup><genome mutation><hCoV19><heavy metal Pb><heavy metal lead><host response><immune function><immune system response><immunoresponse><immunosuppressed patient><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><mRNA vaccine><mRNA-1273><mRNA-based vaccine><mRNA1273><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><novel><operation><operations><outbreak of SARS-CoV-2><post SARS-CoV-2 infection><prevent><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><preventing><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><randomisation><randomization><randomly assigned><response><safety assessment><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 negative><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><symptomatic COVID-19><symptomatic COVID19><symptomatic coronavirus disease 2019><transmission process><trial comparing><vaccination study><vaccination trial><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine efficacy><vaccine for novel coronavirus><vaccine study><vaccine trial><variants of concern>