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Article ; Online: Zika vaccines: can we solve one problem without creating another one?

Castanha, Priscila M S / Marques, Ernesto T A

2021 Volume 21, Issue 9, Page(s) 1198–1200

MeSH term(s)	Humans ; Vaccines ; Zika Virus/immunology ; Zika Virus Infection/prevention & control
Chemical Substances	Vaccines
Language	English
Publishing date	2021-05-18
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(20)30768-4
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Article ; Online: Vaccine development during global epidemics: the Zika experience.

Castanha, Priscila M S / Marques, Ernesto T A

The Lancet. Infectious diseases

2020 Volume 20, Issue 9, Page(s) 998–999

MeSH term(s)	Double-Blind Method ; Epidemics ; Humans ; Zika Virus ; Zika Virus Infection/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-05-06
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(20)30360-1
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Article ; Online: A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development.

Castanha, Priscila M S / Marques, Ernesto T A

Viruses

2020 Volume 12, Issue 12

Abstract: The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a ... ...

Abstract	The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a safe and effective Zika vaccine. Multiple vaccine platforms, including purified inactivated virus, nucleic acid vaccines, live-attenuated vaccines, and viral-vectored vaccines, have advanced to human clinical trials. In this review, we discuss the recent advances in the field of Zika vaccine development and the challenges for future clinical efficacy trials. We provide a brief overview on Zika vaccine platforms in the pipeline before summarizing the vaccine candidates in clinical trials, with a focus on recent, promising results from vaccine candidates that completed phase I trials. Despite low levels of transmission during recent years, ZIKV has become endemic in the Americas and the potential of large Zika outbreaks remains real. It is important for vaccine developers to continue developing their Zika vaccines, so that a potential vaccine is ready for deployment and clinical efficacy trials when the next ZIKV outbreak occurs.
MeSH term(s)	Clinical Trials as Topic ; Disease Outbreaks ; Drug Evaluation, Preclinical ; Global Health ; Humans ; Outcome Assessment, Health Care ; Public Health Surveillance ; Vaccines, Attenuated/immunology ; Vaccines, Synthetic/immunology ; Vaccinology/methods ; Viral Vaccines/immunology ; Zika Virus/immunology ; Zika Virus Infection/epidemiology ; Zika Virus Infection/immunology ; Zika Virus Infection/prevention & control ; Zika Virus Infection/virology
Chemical Substances	Vaccines, Attenuated ; Vaccines, Synthetic ; Viral Vaccines
Language	English
Publishing date	2020-11-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12121371
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Postintervention Immunological and Entomological Survey of Lymphatic Filariasis in the City of Olinda, Brazil, 2015-2016.

Ramesh, Anita / Oliveira, Paula / Cameron, Mary / Castanha, Priscila M S / Walker, Thomas / Lenhart, Audrey / Impoinvil, Lucy / Alexander, Neal / Medeiros, Zulma / Sá, André / Rocha, Abraham / Souza, Wayner V / Maciel, Amélia / Braga, Cynthia

The American journal of tropical medicine and hygiene

2024 Volume 110, Issue 3, Page(s) 470–482

Abstract: Lymphatic filariasis (LF) is a leading cause of disability due to infectious disease worldwide. The Recife Metropolitan Region (RMR) is the only remaining focus of LF in Brazil, where the parasite Wuchereria bancrofti is transmitted solely by the ... ...

Abstract	Lymphatic filariasis (LF) is a leading cause of disability due to infectious disease worldwide. The Recife Metropolitan Region (RMR) is the only remaining focus of LF in Brazil, where the parasite Wuchereria bancrofti is transmitted solely by the mosquito Culex quinquefasciatus. This study reports the results of transmission assessment surveys and molecular xenomonitoring in the city of Olinda, RMR, after nearly 15 years (2015-2016) of interventions for LF elimination. Participants were screened for W. bancrofti antigen via immunochromatographic card tests (ICT) in: 1) door-to-door surveys conducted for all children aged 5-7 years from 4 out of 17 intervention areas treated with at least five annual doses of mass drug administration (MDA), and 2) a two-stage cluster sampling survey of residents aged 5 years and older in non-MDA areas. Mosquitoes were collected via handheld aspirators in four MDA areas, differentiated by species, sex, and physiological status, pooled into groups of up to 10 blood-fed, semigravid, and gravid mosquitoes, and screened for W. bancrofti infection by real-time quantitative polymerase chain reaction (RT-qPCR). All 1,170 children from MDA areas and the entire population sample of 990 residents in non-MDA areas were ICT negative. In MDA areas, a total of 3,152 female Cx. quinquefasciatus mosquitoes in 277 households (range, 0-296 mosquitoes per house) were collected via aspiration. RT-qPCR of 233 pools of mosquitos were negative for W. bancrofti RNA; an independent reference laboratory confirmed these results. These results provide evidence that LF transmission has been halted in this setting.
MeSH term(s)	Child ; Animals ; Humans ; Female ; Elephantiasis, Filarial/epidemiology ; Elephantiasis, Filarial/prevention & control ; Elephantiasis, Filarial/drug therapy ; Brazil/epidemiology ; Culex/genetics ; Wuchereria bancrofti ; Culicidae
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.23-0174
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Article: Vaccine development during global epidemics: the Zika experience

Castanha, Priscila M S / Marques, Ernesto T A

Lancet Infect Dis

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #186283
Database	COVID19

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Article ; Online: SARS-CoV-2 mRNA Vaccines Induce Greater Complement Activation and Decreased Viremia and Nef Antibodies in Men With HIV-1.

Tuttle, Dylan J / Castanha, Priscila M S / Nasser, Amro / Wilkins, Maris S / Galarza, Tamara García / Alaoui-El-Azher, Mounia / Cuff, Deirdre E / Chhibbar, Prabal / Das, Jishnu / Li, Yijia / Barratt-Boyes, Simon M / Mailliard, Robbie B / Sluis-Cremer, Nicolas / Rinaldo, Charles R / Marques, Ernesto T A

The Journal of infectious diseases

2023 Volume 229, Issue 4, Page(s) 1147–1157

Abstract: ... mRNA vaccines in PWH and their impact on HIV-1.: Methods: We quantified anti-S immunoglobulin G (IgG ... plasma RNA.: Results: MWH had lower anti-S IgG binding and neutralizing antibodies against the 3 ...

Abstract	Background: Immune dysregulation in people with human immunodeficiency virus-1 (PWH) persists despite potent antiretroviral therapy and, consequently, PWH tend to have lower immune responses to licensed vaccines. However, limited information is available about the impact of mRNA vaccines in PWH. This study details the immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in PWH and their impact on HIV-1. Methods: We quantified anti-S immunoglobulin G (IgG) binding and neutralization of 3 SARS-CoV-2 variants of concern and complement activation in blood from virally suppressed men with HIV-1 (MWH) and men without HIV-1 (MWOH), and the characteristics that may impact the vaccine immune responses. We also studied antibody levels against HIV-1 proteins and HIV-1 plasma RNA. Results: MWH had lower anti-S IgG binding and neutralizing antibodies against the 3 variants compared to MWOH. MWH also produced anti-S1 antibodies with a 10-fold greater ability to activate complement and exhibited higher C3a blood levels than MWOH. MWH had decreased residual HIV-1 plasma viremia and anti-Nef IgG approximately 100 days after immunization. Conclusions: MWH respond to SARS-CoV-2 mRNA vaccines with lower antibody titers and with greater activation of complement, while exhibiting a decrease in HIV-1 viremia and anti-Nef antibodies. These results suggest an important role of complement activation mediating protection in MWH.
MeSH term(s)	Humans ; Male ; Antibodies, Neutralizing ; Antibodies, Viral ; Complement Activation ; COVID-19/prevention & control ; COVID-19 Vaccines/therapeutic use ; HIV Seropositivity ; HIV-1/immunology ; Immunoglobulin G ; mRNA Vaccines/therapeutic use ; SARS-CoV-2 ; Viremia
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin G ; mRNA Vaccines
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad544
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Article ; Online: Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures.

iScience

2023 Volume 26, Issue 10, Page(s) 107830

Abstract: Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 ... ...

Abstract	Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 infection in cynomolgus macaques. An inhaled aerosol virus dose of 5.1 log
Language	English
Publishing date	2023-09-06
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107830
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Herpesvirus Infections in the Human Brain: A Neural Cell Model of the Complement System Derived from Induced Pluripotent Stem Cells.

Marques, Ernesto T A / Demers, Matthew / D'Aiuto, Leonardo / Castanha, Priscila M S / Yeung, Jason / Wood, Joel A / Chowdari, Kodavali V / Zheng, Wenxiao / Yolken, Robert H / Nimgaonkar, Vishwajit L

Current topics in behavioral neurosciences

2022 Volume 61, Page(s) 243–264

Abstract: ... induced pluripotent stem cells were differentiated into neuronal (hi-N) and microglial (hi-M) cells that were cultured ... differ by cell type and co-culture conditions, with evidence for cellular crosstalk in co-cultures. Hi-N and hi-M ... proteins. hi-N cells produce complement factor 4 (C4) and factor B (FB), whereas hi-M cells produce ...

Abstract	Background: Herpesviruses alter cognitive functions in humans following acute infections; progressive cognitive decline and dementia have also been suggested. It is important to understand the pathogenic mechanisms of such infections. The complement system - comprising functionally related proteins integral for systemic innate and adaptive immunity - is an important component of host responses. The complement system has specialized functions in the brain. Still, the dynamics of the brain complement system are still poorly understood. Many complement proteins have limited access to the brain from plasma, necessitating synthesis and specific regulation of expression in the brain; thus, complement protein synthesis, activation, regulation, and signaling should be investigated in human brain-relevant cellular models. Cells derived from human-induced pluripotent stem cells (hiPSCs) could enable tractable models. Methods: Human-induced pluripotent stem cells were differentiated into neuronal (hi-N) and microglial (hi-M) cells that were cultured with primary culture human astrocyte-like cells (ha-D). Gene expression analyses and complement protein levels were analyzed in mono- and co-cultures. Results: Transcript levels of complement proteins differ by cell type and co-culture conditions, with evidence for cellular crosstalk in co-cultures. Hi-N and hi-M cells have distinct patterns of expression of complement receptors, soluble factors, and regulatory proteins. hi-N cells produce complement factor 4 (C4) and factor B (FB), whereas hi-M cells produce complement factor 2 (C2) and complement factor 3 (C3). Thus, neither hi-N nor hi-M cells can form either of the C3-convertases - C4bC2a and C3bBb. However, when hi-N and hi-M cells are combined in co-cultures, both types of functional C3 convertase are produced, indicated by elevated levels of the cleaved C3 protein, C3a. Conclusions: hiPSC-derived co-culture models can be used to study viral infection in the brain, particularly complement receptor and function in relation to cellular "crosstalk." The models could be refined to further investigate pathogenic mechanisms.
MeSH term(s)	Humans ; Induced Pluripotent Stem Cells/metabolism ; Complement C3/metabolism ; Neurons/metabolism ; Complement C3-C5 Convertases/metabolism ; Brain/metabolism ; Herpesviridae Infections/metabolism
Chemical Substances	Complement C3 ; Complement C3-C5 Convertases (EC 3.4.21.-)
Language	English
Publishing date	2022-08-18
Publishing country	Germany
Document type	Journal Article
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2022_383
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Article ; Online: Two-year Decay of Zika Virus Neutralizing Antibodies in People Living in an Endemic Region in Brazil.

Magalhaes, Tereza / Morais, Clarice N L / Azevedo, Elisa A N / Jacques, Iracema J A A / Castanha, Priscila M S / Cordeiro, Marli T / Braga, Cynthia / Jaenisch, Thomas / Marques, Ernesto T A / Foy, Brian D

The American journal of tropical medicine and hygiene

2022 Volume 107, Issue 1, Page(s) 186–189

Abstract: It is currently not clear whether humoral immunity to Zika virus (ZIKV) elicited upon natural ZIKV infection is long-lasting. In addition, cross-reactivity of anti-ZIKV antibodies with antigenically related dengue viruses (DENV) may have biological ... ...

Abstract	It is currently not clear whether humoral immunity to Zika virus (ZIKV) elicited upon natural ZIKV infection is long-lasting. In addition, cross-reactivity of anti-ZIKV antibodies with antigenically related dengue viruses (DENV) may have biological implications in nonnaive individuals who subsequently acquire a heterotypic infection. Cross-reactive humoral immunity between ZIKV and DENV also complicates the interpretation of serological tests to evaluate previous exposure to either virus. Here, we have measured the 2-year decay of ZIKV neutralizing antibodies in people living in a ZIKV/DENV endemic area in Brazil who were identified as having an acute infection (group 1) or past (but recent) infection (group 2) with ZIKV in 2015-16. The titers of neutralizing antibodies to ZIKV decreased 9.1 and 2.3 times in groups 1 and 2, respectively. We also show that the plaque reduction neutralization assay (PRNT) is a reliable method to measure past exposure to ZIKV in coendemic areas.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; Brazil/epidemiology ; Cross Reactions ; Dengue ; Dengue Virus ; Humans ; Zika Virus ; Zika Virus Infection
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2022-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.21-1279
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Article ; Online: Reciprocal immune enhancement of dengue and Zika virus infection in human skin.

Castanha, Priscila M S / Erdos, Geza / Watkins, Simon C / Falo, Louis D / Marques, Ernesto T A / Barratt-Boyes, Simon M

JCI insight

2020 Volume 5, Issue 3

Abstract: Dengue virus (DENV) and Zika virus (ZIKV) are closely related mosquito-borne flaviviruses that co-circulate in tropical regions and constitute major threats to global human health. Whether preexisting immunity to one virus affects disease caused by the ... ...

Abstract	Dengue virus (DENV) and Zika virus (ZIKV) are closely related mosquito-borne flaviviruses that co-circulate in tropical regions and constitute major threats to global human health. Whether preexisting immunity to one virus affects disease caused by the other during primary or secondary infections is unknown but is critical in preparing for future outbreaks and predicting vaccine safety. Using a human skin explant model, we show that DENV-3 immune sera increased recruitment and infection of Langerhans cells, macrophages, and dermal dendritic cells following inoculation with DENV-2 or ZIKV. Similarly, ZIKV immune sera enhanced infection with DENV-2. Immune sera increased migration of infected Langerhans cells to the dermis and emigration of infected cells out of skin. Heterotypic immune sera increased viral RNA in the dermis almost 10-fold and reduced the amount of virus required to infect a majority of myeloid cells by 100- to 1000-fold. Enhancement was associated with cross-reactive IgG and induction of IL-10 expression and was mediated by both CD32 and CD64 Fcγ receptors. These findings reveal that preexisting heterotypic immunity greatly enhances DENV and ZIKV infection, replication, and spread in human skin. This relevant tissue model will be valuable in assessing the efficacy and risk of dengue and Zika vaccines in humans.
MeSH term(s)	Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Cross Reactions/immunology ; Dengue/immunology ; Dengue Virus/immunology ; Humans ; Immune Sera ; Skin/virology ; Zika Virus/immunology ; Zika Virus Infection/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immune Sera
Language	English
Publishing date	2020-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.133653
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