Mariana Baz

Mariana Baz
National Institutes of Health | NIH · Laboratory of Infectious Diseases

PhD

About

58
Publications
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1,854
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Publications

Publications (58)
Article
Full-text available
Early predictions forecasted large numbers of severe acute respiratory syndrome coronavirus (SARS-CoV-2) cases and associated deaths in Africa. To date, Africa has been relatively spared. Various hypotheses were postulated to explain the lower than anticipated impact on public health in Africa. However, the contribution of pre-existing immunity is...
Article
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The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently needs effective antivirals. After over 2 years since the beginning of the pandemic, only a few FDA approved therapeutic options are available to treat the population. Combination therapies have become a standar...
Article
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A vaccine candidate to SARS-CoV-2 was constructed by coupling the viral receptor binding domain (RBD) to the surface of the papaya mosaic virus (PapMV) nanoparticle (nano) to generate the RBD-PapMV vaccine. Immunization of mice with the coupled RBD-PapMV vaccine enhanced the antibody titers and the T-cell mediated immune response directed to the RB...
Article
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Antiviral drugs are an important measure of control for influenza in the population, particularly for those that are severely ill or hospitalised. The neuraminidase inhibitor (NAI) class of drugs, including oseltamivir, have been the standard of care (SOC) for severe influenza illness for many years. The approval of drugs with novel mechanisms of a...
Preprint
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Importance Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. We present detailed immunological evidence to...
Article
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The polymerase acidic (PA) I38T substitution is a dominant marker of resistance to baloxavir. We evaluated the impact of I38T on the fitness of a contemporary influenza A(H3N2) virus. Influenza A/Switzerland/9715293/2013 (H3N2) wild-type (WT) virus and its I38T mutant were rescued by reverse genetics. Replication kinetics were compared using ST6Gal...
Article
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We performed viral culture of respiratory specimens in 118 SARS-CoV-2 infected healthcare workers (HCW), approximately 2 weeks after symptom onset. Only one HCW (0.8%) had a positive culture. No factors for prolonged viral shedding were identified. Infectivity is resolved in nearly all HCWs approximately 2 weeks after symptom onset.
Article
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The prolonged treatment of immunosuppressed (IS) individuals with anti-influenza monotherapies may lead to the emergence of drug-resistant variants. Herein, we evaluated oseltamivir and polymerase inhibitors combinations against influenza A/H3N2 infections in an IS mouse model. Mice were IS with cyclophosphamide and infected with 3 × 103 PFU of a m...
Article
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Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prev...
Chapter
Zika virus (ZIKV) is an important pathogen transmitted to humans by the mosquito vector Aedes aegypti. ZIKV is able to infect several tissues and organs and, importantly, has been associated with microcephaly and central nervous system abnormalities in fetuses and newborn babies of mothers exposed to ZIKV during pregnancy, as well as neurological d...
Article
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The mouse is the most widely used animal model for influenza virus research. However, the susceptibility of mice to seasonal influenza virus depends on the strain of mouse and on the strain of the influenza virus. Seasonal A/H3N2 influenza viruses do not replicate well in mice and therefore they need to be adapted to this animal model. In this stud...
Article
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Background Baloxavir marboxil (BXM), a cap-dependent endonuclease inhibitor, has been recently approved in the United States for the treatment of influenza infections. It is superior to oseltamivir for reducing the time of viral shedding but is reported to have a low barrier of resistance. We sought to evaluate the viral fitness of the predominant...
Article
Full-text available
The I38T PA substitution associated with baloxavir resistance did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses in vitro. Similarly, the wild-type and its I38T mutant induced similar weight loss with comparable lung titers in a mouse model. Abstract Background: Baloxavir is a cap-dependent inhibitor of the polymerase acid (...
Article
Background: Baloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence. Methods: In...
Article
Full-text available
In 1947, Zika virus (ZIKV), a mosquito-borne flavivirus was identified in Uganda and subsequently spread to Asia and the Pacific regions. In 2015, it was introduced in Brazil causing an important social and sanitary alarm due to its increased virulence and rapid dissemination. Importantly, ZIKV infections have been associated with severe neurologic...
Article
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Immunosuppressed individuals can shed influenza virus for prolonged periods of time, leading to the frequent emergence of antiviral resistance. We evaluated the benefits of oseltamivir and favipiravir combination therapy compared to single antiviral agents and monitored the emergence of drug-resistant variants in a pharmacologically immunosuppresse...
Article
Neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) are expected to occur at framework or catalytic residues of the NA enzyme. Numerous clinical and in vitro reports already described NAI-resistant A(H1N1)pdm09 variants harboring various framework NA substitutions. By contrast, variants with NA catalytic changes remain poorly...
Article
Toll-like receptors and RNA helicases are involved in the control of RNA virus infection through production of type I interferons (IFNs). To delineate the relative contributions of these signalling pathways in the innate immune response and the control of Zika virus (ZIKV) pathogenesis, the impact of a deficiency in TRIF and/or IPS-1 adaptor protei...
Article
Background: Zika virus (ZIKV), a previously neglected mosquito-borne virus, is prompting worldwide concern because of its connection with congenital defects, Guillain-Barré syndrome, meningoencephalitis and myelitis in infected individuals. However, no specific antiviral therapy is available at present. In this study, we investigated the in vitro...
Article
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Influenza A(H1N1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. By using escape mutants, we previously identified six haemagglutinin (HA) changes (T80R, G143E, G158E, N159D, K166E and A198E) that were located within antigenic sites. Combinations of these mutations were introduced...
Article
We have developed pandemic live attenuated influenza vaccines (pLAIVs) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (clade 2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt, which prompted updating of t...
Article
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New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corres...
Article
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H3N8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. However, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys and seals and therefore pose a threat to humans. A live attenuated cold-adapted (ca) H3N8 vaccine virus was generated b...
Article
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Unlabelled: Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have...
Article
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The evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. Herein, we assessed the evolution of neuraminidase (NA) and hemagglutinin (HA) genes of influenza A/WSN/33 (H1N1) and A/Victoria/3/75 (H3N2) viruses recovered from lungs of experimentally-infected BALB/c mice receiving su...
Article
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Unlabelled: Live attenuated H7N9 influenza vaccine viruses that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the newly emerged wild-type (wt) A/Anhui/1/2013 (H7N9) and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (AA ca) were generated by reverse genetics. The reassortant vir...
Article
The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemi...
Article
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Since it is difficult to predict which influenza virus subtype will cause an influenza pandemic, it is important to prepare influenza virus vaccines against different subtypes and evaluate the safety and immunogenicity of candidate vaccines in preclinical and clinical studies prior to a pandemic. In addition to infecting humans, H3 influenza viruse...
Article
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We looked for cross-reactive antibodies in 122 persons with paired serum samples collected during the 2009 pandemic of influenza virus A(H1N1)pdm09. Eight (12%) of 67 persons with A(H1N1)pdm09 infection confirmed by reverse transcription PCR and/or serology also seroconverted to the seasonal A/Brisbane/59/2007 (H1N1) virus, compared with 1 (2%) of...
Article
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Influenza A/H3N2 viruses have caused the most severe epidemics since 1968 despite current immunization programs with inactivated vaccines. We undertook a side-by-side preclinical evaluation of different adjuvants (Alum, AS03, and Protollin) and routes of administration (intramuscular [i.m.] and intranasal [i.n.]) for assessing their effect on the i...
Article
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Serology improves influenza diagnosis by capturing cases missed by reverse transcriptase PCR (RT-PCR). We prospectively evaluated microneutralization and hemagglutination inhibition assays for 2009 influenza A (H1N1) virus diagnosis among 24 RT-PCR-confirmed cases and 98 household contacts. Compared to hemagglutination inhibition, microneutralizati...
Article
We evaluated the efficacy and tolerability of a single dose of the split virion AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in 84 HIV-1 infected individuals. Antibody titers were determined by hemagglutination inhibition assay and by microneutralization. Vaccine was well tolerated. At 21 days post vaccination, 56 (67%) pat...
Article
The H275Y neuraminidase mutation conferring oseltamivir resistance has been reported in several pandemic A/H1N1 (pH1N1) isolates. We sought to evaluate transmission of this mutant virus through the direct contact and the airborne (aerosol and droplet) routes in the ferret model. Groups of four ferrets were infected with either wild-type (WT) or ose...
Article
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Characterizing household transmission of the 2009 pandemic A/H1N1 influenza virus (pH1N1) is critical for the design of effective public health measures to mitigate spread. Our objectives were to estimate the secondary attack rates (SARs), the proportion of asymptomatic infections, and risk factors for pH1N1 transmission within households on the ba...
Data
Weight loss of ferrets infected with wild-type (WT) or H274Y mutant isolates of pH1N1. (0.15 MB TIF)
Data
Lung viral titers of mice infected with wild-type (WT) or H274Y mutant isolates of pH1N1. (0.23 MB TIF)
Data
Hemagglutination inhibition titers for pH1N1 (A/California/7/09) and seasonal A/H1N1 (A/Brisbane/59/07) in ferrets infected with wild-type and H274Y mutant pH1N1 viruses. (0.04 MB DOC)
Data
Lung histopathology of mice infected with wild-type (WT) or H274Y mutant isolates of pH1N1. (5.84 MB TIF)
Data
Lung cytokines/chemokines expression in mice infected with wild-type (WT) or H274Y mutant isolates of pH1N1. (0.41 MB TIF)
Article
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The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible pH1N1 clinical isolates that dif...
Article
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The viral fitness of neuraminidase inhibitor (NAI)-resistant influenza viruses is believed to be impaired. Unexpectedly, an oseltamivir-resistant A(H1N1) variant containing the H274Y neuraminidase (NA) mutation recently disseminated worldwide, suggesting that the replication and virulence properties of this mutant virus were not compromised. In vit...
Article
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Introducción: en nuestro país no existen trabajos sistemáticos relativos a la incidencia de virus que provoquen encefalitis y meningitis. Sí existen trabajos realizados en las décadas de 1960 y 1970 sobre seroprevalencia de arbovirus y poliovirus. Mediante la técnica de reacción en cadena de polimerasa (PCR) aplicada al líquido cefalorraquídeo (LCR...
Article
To the Editor: Neuraminidase inhibitors (oseltamivir and zanamivir) are recommended for treatment of severe illness caused by the 2009 pandemic influenza A (H1N1) virus, and their use has also been advocated for postexposure prophylaxis in high-risk persons.1 We report the emergence of an oseltamivir-resistant virus in a familial cluster of infecti...
Article
Neuraminidase (NA) mutations responsible for influenza resistance to oseltamivir vary according to the NA subtype; in influenza A/H3N2 viruses, NA-gene mutations occur predominantly at codons E119 and R292. In an oseltamivir-resistant influenza A/H3N2 virus isolated from an immunocompromised child after 107 days of cumulative treatment, the NA gene...
Article
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The new oral neuraminidase (NA) inhibitor A-322278 was evaluated in mice infected with influenza A/H1N1 wild-type virus or the oseltamivir-resistant (H274Y mutant) virus. A-322278 decreased mortality rates and lung virus titers significantly more than oseltamivir in mice infected with the NA H274Y mutant when therapy was started 4 h before or even...
Article
With the emergence of highly virulent influenza viruses and the consequent risk of pandemics, new approaches to designing universal influenza vaccines are urgently needed. In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccin...
Article
Clinical use of the neuraminidase inhibitor (NAI) oseltamivir has been associated with the emergence of viral resistance resulting from subtype-specific neuraminidase (NA) mutations. In this study, we evaluated the impact of the most frequent oseltamivir-resistant NA mutations including E119V, H274Y, R292K and N294S on the susceptibility profile to...
Article
There is a limited information with regard to the neuraminidase (NA) mutations conferring resistance to peramivir and zanamivir in the influenza N1 background. In this study, an influenza A/WSN/33 (H1N1) recombinant virus was passaged under peramivir or zanamivir pressure. The peramivir-selected variant had a H274Y mutation in the neuraminidase (NA...
Article
Monitoring antigenic and genetic variations of circulating influenza viruses is critical for the selection of annual vaccine strains. In order to gain insight into the molecular evolution of Influenza B viruses (IBV) isolated in Uruguay in 2002 and 2005 outbreaks, antigenic and phylogenetic studies were carried out for the Hemagglutinin (HA) gene....
Article
Development of influenza drug resistance is an important problem in immunocompromised children that could result in treatment failure and viral transmission to others. A total of 17 influenza A/H3N2 isolates were recovered over a period of 1 year from an immunocompromised child who was initially treated with oseltamivir and then with amantadine and...
Article
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Subtype-specific neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) have been reported during in vitro passages and in clinic. In this study, we evaluated the impact of various NA mutations (E119A/G/V, H274Y, R292K and N294S) on the susceptibility profiles to different NAIs (oseltamivir, zanamivir and peramivir) using recomb...
Article
A new human coronavirus (HCoV), HCoV-NL, was recently reported for Dutch patients with acute respiratory tract infections (ARTI). Little information is available on the incidence, clinical manifestations and epidemiologic features of HCoV-NL infections. We performed a prospective study of symptomatic (case subjects with ARTI) and asymptomatic (cont...
Article
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Thèse (M.Sc.)--Université Laval, 2006. Bibliogr.: f. 133-151.

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