Ralph Baric - Academia.edu (original) (raw)

Papers by Ralph Baric

Research paper thumbnail of GII.4 Human Norovirus: Surveying the Antigenic Landscape

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2019

Research paper thumbnail of Norovirus vaccine induces a cross-genotype protective immune response

International Journal of Infectious Diseases, Dec 1, 2020

Research paper thumbnail of Efficacy of pediatric SARS-CoV-2 vaccines against high-dose B.1.617.2 challenge one year after vaccination of infant rhesus macaques

Journal of Immunology, May 1, 2022

To advance SARS-CoV-2 vaccines in infants younger than 5 years, we tested the efficacy of two SAR... more To advance SARS-CoV-2 vaccines in infants younger than 5 years, we tested the efficacy of two SARS-CoV-2 vaccine platforms against challenge with the delta variant one year after immunization of infant rhesus macaques (RM). Infant RMs (n=8/ group; 2 month-old) were immunized intramuscularly at weeks 0 and 4 with 30 mg stabilized prefusion SARS-CoV-2 S-2P spike (S) protein (Washington strain) encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or 15 mg S protein mixed with 3M-052 in stable emulsion (Protein). At 1 year, vaccinated and age-matched unvaccinated RM (n=8) were challenged intranasally (106 pfu) and intratracheally (2×106 pfu) with B.1.617.2. Lung pathology was blindly assessed on day 7. Viral RNA copies of the N gene (vRNA) were measured by qPCR in nasal and pharyngeal swabs. Severe lung pathology was observed in 7 of 8 controls compared to 1 of 8 or 0 of 8 RM in the mRNA-LNP or protein group, respectively. On days 2 and 4, vRNA copies/ml were significantly higher in pharyngeal swabs of control RM (day 2: 4.2p> Supported by grants from NIH PO1 AI117915

Research paper thumbnail of Disulfide stabilization of human norovirus GI.1 virus-like particles focuses immune response toward blockade epitopes

npj vaccines, Dec 14, 2020

Research paper thumbnail of Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus

Research paper thumbnail of Norwalk virus: How infectious is it?

Journal of Medical Virology, 2008

Research paper thumbnail of Norovirus-Specific CD8+ T Cell Responses in Human Blood and Tissues

Cellular and molecular gastroenterology and hepatology, 2021

Research paper thumbnail of A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters

Journal of Virology, Aug 1, 2008

Research paper thumbnail of Norovirus pathogenesis: mechanisms of persistence and immune evasion in human populations

Immunological Reviews, Oct 1, 2008

Research paper thumbnail of Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge one year later

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2022

Research paper thumbnail of Preexisting Heterotypic Ligand-blocking Antibody Does Not Protect Against Genogroup II Norovirus Episodes in Young Children

Journal of the Pediatric Infectious Diseases Society

A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibo... more A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibodies provide cross-protection within the GII genogroup. We found that almost one-half of children who experienced a norovirus GII episode had preexisting antibodies heterotypic to the infecting genotype; therefore, these antibodies did not provide cross-protection.

Research paper thumbnail of Predictors of human norovirus infection and immunity (133.52)

Journal of Immunology, Apr 1, 2009

Research paper thumbnail of Sars-cov-2 vaccines induce durable neutralizing antibodies in infant rhesus macaques

Topics in antiviral medicine, 2021

Research paper thumbnail of Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum

The Journal of Infectious Diseases, 2022

Background Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis... more Background Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis. We evaluated the use of a new GII.2 inoculum in a human challenge. Methods Forty-four healthy adults (36 secretor-positive and 8 secretor-negative for histo-blood group antigens) were challenged with ascending doses of a new safety-tested Snow Mountain virus (SMV) GII.2 norovirus inoculum (1.2 × 104 to 1.2 × 107 genome equivalent copies [GEC]; n = 38) or placebo (n = 6). Illness was defined as diarrhea and/or vomiting postchallenge in subjects with evidence of infection (defined as GII.2 norovirus RNA detection in stool and/or anti-SMV immunoglobulin G [IgG] seroconversion). Results The highest dose was associated with SMV infection in 90%, and illness in 70% of subjects with 10 of 12 secretor-positive (83%) and 4 of 8 secretor-negative (50%) becoming ill. There was no association between prechallenge anti-SMV serum IgG concentration, carbohydrate-binding blockade antibody, or salivary...

Research paper thumbnail of Monoclonal Antibody-Based Antigenic

Research paper thumbnail of Secretor Status Strongly Influences the Incidence of Symptomatic Norovirus Infection in a Genotype-Dependent Manner in a Nicaraguan Birth Cohort

The Journal of Infectious Diseases, 2021

Background The role of histo-blood group on the burden and severity of norovirus gastroenteritis ... more Background The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. Methods Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. Results Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor ...

Research paper thumbnail of Author Correction: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Research paper thumbnail of CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infecti... more Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. Thebona fidereceptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infectionin vitro. Here we explored whether CD300lf is the sole physiologic receptorin vivoand whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strainsin vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responsesin vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. However, after high dose intraperitoneal challenge with MNoV inCd300lf−/−Stat1−/−mice a single amino acid mutation in the ...

Research paper thumbnail of SARS-like WIV1-CoV poised for human emergence

Proceedings of the National Academy of Sciences of the United States of America, Jan 14, 2016

Outbreaks from zoonotic sources represent a threat to both human disease as well as the global ec... more Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored...

Research paper thumbnail of Correction: Corrigendum: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Research paper thumbnail of GII.4 Human Norovirus: Surveying the Antigenic Landscape

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2019

Research paper thumbnail of Norovirus vaccine induces a cross-genotype protective immune response

International Journal of Infectious Diseases, Dec 1, 2020

Research paper thumbnail of Efficacy of pediatric SARS-CoV-2 vaccines against high-dose B.1.617.2 challenge one year after vaccination of infant rhesus macaques

Journal of Immunology, May 1, 2022

To advance SARS-CoV-2 vaccines in infants younger than 5 years, we tested the efficacy of two SAR... more To advance SARS-CoV-2 vaccines in infants younger than 5 years, we tested the efficacy of two SARS-CoV-2 vaccine platforms against challenge with the delta variant one year after immunization of infant rhesus macaques (RM). Infant RMs (n=8/ group; 2 month-old) were immunized intramuscularly at weeks 0 and 4 with 30 mg stabilized prefusion SARS-CoV-2 S-2P spike (S) protein (Washington strain) encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or 15 mg S protein mixed with 3M-052 in stable emulsion (Protein). At 1 year, vaccinated and age-matched unvaccinated RM (n=8) were challenged intranasally (106 pfu) and intratracheally (2×106 pfu) with B.1.617.2. Lung pathology was blindly assessed on day 7. Viral RNA copies of the N gene (vRNA) were measured by qPCR in nasal and pharyngeal swabs. Severe lung pathology was observed in 7 of 8 controls compared to 1 of 8 or 0 of 8 RM in the mRNA-LNP or protein group, respectively. On days 2 and 4, vRNA copies/ml were significantly higher in pharyngeal swabs of control RM (day 2: 4.2p> Supported by grants from NIH PO1 AI117915

Research paper thumbnail of Disulfide stabilization of human norovirus GI.1 virus-like particles focuses immune response toward blockade epitopes

npj vaccines, Dec 14, 2020

Research paper thumbnail of Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus

Research paper thumbnail of Norwalk virus: How infectious is it?

Journal of Medical Virology, 2008

Research paper thumbnail of Norovirus-Specific CD8+ T Cell Responses in Human Blood and Tissues

Cellular and molecular gastroenterology and hepatology, 2021

Research paper thumbnail of A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters

Journal of Virology, Aug 1, 2008

Research paper thumbnail of Norovirus pathogenesis: mechanisms of persistence and immune evasion in human populations

Immunological Reviews, Oct 1, 2008

Research paper thumbnail of Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge one year later

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2022

Research paper thumbnail of Preexisting Heterotypic Ligand-blocking Antibody Does Not Protect Against Genogroup II Norovirus Episodes in Young Children

Journal of the Pediatric Infectious Diseases Society

A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibo... more A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibodies provide cross-protection within the GII genogroup. We found that almost one-half of children who experienced a norovirus GII episode had preexisting antibodies heterotypic to the infecting genotype; therefore, these antibodies did not provide cross-protection.

Research paper thumbnail of Predictors of human norovirus infection and immunity (133.52)

Journal of Immunology, Apr 1, 2009

Research paper thumbnail of Sars-cov-2 vaccines induce durable neutralizing antibodies in infant rhesus macaques

Topics in antiviral medicine, 2021

Research paper thumbnail of Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum

The Journal of Infectious Diseases, 2022

Background Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis... more Background Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis. We evaluated the use of a new GII.2 inoculum in a human challenge. Methods Forty-four healthy adults (36 secretor-positive and 8 secretor-negative for histo-blood group antigens) were challenged with ascending doses of a new safety-tested Snow Mountain virus (SMV) GII.2 norovirus inoculum (1.2 × 104 to 1.2 × 107 genome equivalent copies [GEC]; n = 38) or placebo (n = 6). Illness was defined as diarrhea and/or vomiting postchallenge in subjects with evidence of infection (defined as GII.2 norovirus RNA detection in stool and/or anti-SMV immunoglobulin G [IgG] seroconversion). Results The highest dose was associated with SMV infection in 90%, and illness in 70% of subjects with 10 of 12 secretor-positive (83%) and 4 of 8 secretor-negative (50%) becoming ill. There was no association between prechallenge anti-SMV serum IgG concentration, carbohydrate-binding blockade antibody, or salivary...

Research paper thumbnail of Monoclonal Antibody-Based Antigenic

Research paper thumbnail of Secretor Status Strongly Influences the Incidence of Symptomatic Norovirus Infection in a Genotype-Dependent Manner in a Nicaraguan Birth Cohort

The Journal of Infectious Diseases, 2021

Background The role of histo-blood group on the burden and severity of norovirus gastroenteritis ... more Background The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. Methods Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. Results Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor ...

Research paper thumbnail of Author Correction: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Research paper thumbnail of CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infecti... more Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. Thebona fidereceptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infectionin vitro. Here we explored whether CD300lf is the sole physiologic receptorin vivoand whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strainsin vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responsesin vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. However, after high dose intraperitoneal challenge with MNoV inCd300lf−/−Stat1−/−mice a single amino acid mutation in the ...

Research paper thumbnail of SARS-like WIV1-CoV poised for human emergence

Proceedings of the National Academy of Sciences of the United States of America, Jan 14, 2016

Outbreaks from zoonotic sources represent a threat to both human disease as well as the global ec... more Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored...

Research paper thumbnail of Correction: Corrigendum: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence