Document text
Principal Investigator: Kristina De Paris
Organization: DUKE UNIVERSITY
Fiscal Year: 2020
Award: $1,227,827
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
The emergence of the highly-transmissible novel coronavirus SARS-CoV2 has led to a global pandemic of
severe respiratory disease. While elderly individuals and adults with co-morbidities are high risk populations,
coronavirus disease (COVID-19) can occur in individuals across all age groups, including infants. Therefore, it
will be important to develop a vaccine that can be administered in early life and generate long term immunity to
end the COVID19 pandemic. While initial safety testing of vaccine candidates will occur in adult populations,
there are many potential advantages of targeting the vaccine to the pediatric vaccine schedule including high
rates of pediatric vaccine coverage and potential for lifelong immunity. In fact, infants can respond remarkably
well to protein antigens, including the hepatitis B and candidate HIV envelope vaccines, and there is evidence
that HIV-infected infants are better equipped to generate HIV-neutralizing antibodies. Moreover, our previous
work in human and rhesus monkeys has established that infants are able to generate HIV Env vaccine
responses of comparable or higher magnitude to that of adults that persist for months and are able to be
boosted. The parent grant P01 AI117915-06 “Early Life Vaccination to Prevent HIV Acquisition in Adolescence”
aims to assess candidate HIV envelope mRNA and SOSIP trimer vaccines in infant rhesus monkey nonhuman
primate model and determine their efficacy against HIV acquisition in adolescence. As related complementary
studies, we propose to assess the immunogenicity and efficacy of candidate SARS-CoV2 spike (S) protein and
mRNA vaccine candidates in infant rhesus monkeys. We hypothesize that infants can mount effective and
persistent systemic and mucosal antibody responses to SARS-CoV-2 vaccination that will protect
against virus challenge. This work will provide preclinical safety, immunogenicity, and efficacy data on
leading SARS-CoV2 vaccine platforms that can de-risk human trials in pediatric populations and justify
bypassing time consuming and expensive age de-escalation studies. The end of the SARS-CoV2 pandemic
will require high global coverage with a vaccine that prevents viral spread and generates long lasting immunity,
which may best be achieved with a pediatric targeted vaccine.
Terms: <12-20 years old><2019 novel coronavirus><2019-nCoV><21+ years old><7S Gamma Globulin><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adolescence><Adult><Adult Human><Age><Antibodies><Antibody Response><Antigens><Award><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Birth><Blood Plasma><Bypass><COVID><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID19><COVID19 epidemic><COVID19 pandemic><Cell Lineage><Cessation of life><Childhood><CoV disease><CoV emergence><Complement><Complement Proteins><Consumption><Coronaviridae><Coronavirus><Data><Death><Development><Disease><Disease Outbreaks><Disorder><Elderly><Exhibits><HIV><HIV vaccine><HIV/AIDS Vaccines><Hepatitis B><Hepatitis B Infection><Human><Human Immunodeficiency Viruses><IgG><Immune><Immune response><Immune system><Immunes><Immunity><Immunoglobulin G><Immunological response><Immunology><Individual><Infant><Infection><Investigation><LAV-HTLV-III><Length of Life><Life><Longevity><Lung><Lung Respiratory System><Lung diseases><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><MERS><MERS corona virus><MERS coronavirus><MERS coronavirus disease><MERS virus><MERS-CoV><MERS-CoV disease><Macaca><Macaca mulatta><Macaque><Mediating><Memory><Messenger RNA><Mice><Mice Mammals><Middle East Respiratory Syndrome><Middle East Respiratory Syndrome CoV disease><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome coronavirus disease><Middle East Respiratory Syndrome-CoV><Middle Eastern Respiratory Syndrome><Middle Eastern Respiratory Syndrome CoV disease><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome coronavirus disease><Middle Eastern Respiratory Syndrome-CoV><Modeling><Modern Man><Molecular><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Outbreaks><Parents><Parturition><Pathway interactions><Physiology><Plasma><Plasma Serum><Population><Position><Positioning Attribute><Prevention><Proteins><Public Health><Pulmonary Diseases><Pulmonary Disorder><RNA vaccine><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Reticuloendothelial System, Serum, Plasma><Rhesus Macaque><Rhesus Monkey><Risk><SARS><SARS Virus><SARS corona virus><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV disease><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Safety><Schedule><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><Severe acute respiratory syndrome coronavirus 2><Severities><System><Systems Biology><T cell response><Testing><Time><Vaccination><Vaccines><Viral><Viral Diseases><Viral Hepatitis B><Viral Receptor><Virus><Virus Diseases><Virus Receptors><Virus-HIV><Work><Wuhan coronavirus><adolescence (12-20)><adulthood><advanced age><age group><ages><allergic/immunologic body system><allergic/immunologic organ system><base><co-morbid><co-morbidity><combat><comorbidity><corona virus><corona virus disease><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><coronavirus emergence><develop a vaccine><development of a vaccine><developmental><disease of the lung><disorder of the lung><elders><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><experiment><experimental research><experimental study><fighting><geriatric><high risk group><high risk population><host response><human data><human immunodeficiency virus vaccine><immunogen><immunogenicity><immunoresponse><infancy><infant infection><infantile><infected infant><infected neonate><infected newborn><infection with HBV><infection with hepatitis B virus><late life><later life><life span><lifespan><lipid nanoparticle><lung disorder><mRNA><mRNA vaccine><nCoV><neonatal infection><neutralizing antibody><new CoV><new coronavirus><new vaccines><newborn infection><next generation vaccines><non-human primate><nonhuman primate><novel CoV><novel coronavirus><novel vaccines><older adult><older person><pandemic><pandemic disease><parent grant><pathway><pediatric><pre-clinical><pre-clinical safety><preclinical><preclinical safety><predictive signature><prevent><preventing><pulmonary><response><safety testing><senior citizen><serum hepatitis><severe acute respiratory syndrome-CoV><vaccination study><vaccination trial><vaccine candidate><vaccine development><vaccine efficacy><vaccine formulation><vaccine response><vaccine study><vaccine trial><viral infection><virus infection><virus-induced disease>