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Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

Mavigner, Maud ; Raper, Jessica ; Kovacs-Balint, Zsofia ; [et al.]

American Association for the Advancement of Science (AAAS) ; 2018

In: Science Translational Medicine Vol. 10, No. 435 ( 2018-04-04)

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In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 10, No. 435 ( 2018-04-04)

Abstract: The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.

Type of Medium: Online Resource

ISSN: 1946-6234 , 1946-6242

URL: Article

DOI: 10.1126/scitranslmed.aao6975

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2018

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CARACTERIZAÇÃO DA EXPANSÃO DE PLASMOBLASTOS E DO REPERTÓRIO DE ANTICORPOS INDUZIDOS PELA VACINAÇÃO COM 17DD E INFECÇÃO PELO VÍRUS DA FEBRE AMARELA

Marmorato, Mariana P. ; Pedreño‐Lopez, Núria ; Deheinzelin, Joana R. ; [et al.]

Elsevier BV ; 2018

In: The Brazilian Journal of Infectious Diseases Vol. 22 ( 2018-12), p. 6-

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In: The Brazilian Journal of Infectious Diseases, Elsevier BV, Vol. 22 ( 2018-12), p. 6-

Type of Medium: Online Resource

ISSN: 1413-8670

URL: Article

DOI: 10.1016/j.bjid.2018.10.011

Language: Portuguese

Publisher: Elsevier BV

Publication Date: 2018

detail.hit.zdb_id: 2055442-4

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Genomic epidemiology reveals multiple introductions of Zika virus into the United States

Grubaugh, Nathan D. ; Ladner, Jason T. ; Kraemer, Moritz U. G. ; [et al.]

Springer Science and Business Media LLC ; 2017

In: Nature Vol. 546, No. 7658 ( 2017-06-15), p. 401-405

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In: Nature, Springer Science and Business Media LLC, Vol. 546, No. 7658 ( 2017-06-15), p. 401-405

Type of Medium: Online Resource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/nature22400

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TA 1000

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Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 120714-3

detail.hit.zdb_id: 1413423-8

SSG: 11

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Potent Plasmablast-Derived Antibodies Elicited by the National Institutes of Health Dengue Vaccine

Magnani, Diogo M. ; Silveira, Cassia G. T. ; Ricciardi, Michael J. ; [et al.]

American Society for Microbiology ; 2017

In: Journal of Virology Vol. 91, No. 22 ( 2017-11-15)

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In: Journal of Virology, American Society for Microbiology, Vol. 91, No. 22 ( 2017-11-15)

Abstract: Exposure to dengue virus (DENV) is thought to elicit lifelong immunity, mediated by DENV-neutralizing antibodies (nAbs). However, Abs generated by primary infections confer serotype-specific protection, and immunity against other serotypes develops only after subsequent infections. Accordingly, the induction of these nAb responses acquired after serial DENV infections has been a long-sought-after goal for vaccination. Nonetheless, it is still unclear if tetravalent vaccines can elicit or recall nAbs. In this study, we have characterized the responses from a volunteer who had been previously exposed to DENV and was immunized with the live attenuated tetravalent vaccine Butantan-DV, developed by the NIH and Butantan Institute. Eleven days after vaccination, we observed an ∼70-fold expansion of the plasmablast population. We generated 21 monoclonal Abs (MAbs) from singly sorted plasmablasts. These MAbs were the result of clonal expansions and had significant levels of somatic hypermutation (SHM). Nineteen MAbs (90.5%) neutralized at least one DENV serotype at concentrations of 1 μg/ml or less; 6 of the 21 MAbs neutralized three or more serotypes. Despite the tetravalent composition of the vaccine, we observed a neutralization bias in the induced repertoire: DENV3 was targeted by 18 of the 19 neutralizing MAbs (nMAbs). Furthermore, the P3D05 nMAb neutralized DENV3 with extraordinary potency (concentration to achieve half-maximal neutralization [Neut 50 ] = 0.03 μg/ml). Thus, the Butantan-DV vaccine engendered a mature, antigen-selected B cell repertoire. Our results suggest that preexisting responses elicited by a previous DENV3 infection were recalled by immunization. IMPORTANCE The dengue epidemic presents a global public health challenge that causes widespread economic burden and remains largely unchecked by existing control strategies. Successful control of the dengue epidemic will require effective prophylactic and therapeutic interventions. Several vaccine clinical efficacy trials are approaching completion, and the chances that one or more live attenuated tetravalent vaccines (LATVs) will be introduced worldwide is higher than ever. While it is widely accepted that dengue virus (DENV)-neutralizing antibody (nAb) titers are associated with protection, the Ab repertoire induced by LATVs remain uncharacterized. Here, we describe the isolation of potent (Neut 50 〈 0.1 μg/ml) nAbs from a DENV-seropositive volunteer immunized with the tetravalent vaccine Butantan-DV, which is currently in phase III trials.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.00867-17

Language: English

Publisher: American Society for Microbiology

Publication Date: 2017

detail.hit.zdb_id: 1495529-5

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Rectal Acquisition of Simian Immunodeficiency Virus (SIV) SIVmac239 Infection despite Vaccine-Induced Immune Responses against the Entire SIV Proteome

Martins, Mauricio A. ; Gonzalez-Nieto, Lucas ; Ricciardi, Michael J. ; [et al.]

American Society for Microbiology ; 2020

In: Journal of Virology Vol. 94, No. 24 ( 2020-11-23)

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In: Journal of Virology, American Society for Microbiology, Vol. 94, No. 24 ( 2020-11-23)

Abstract: Given the complex biology of human immunodeficiency virus (HIV) and its remarkable capacity to evade host immune responses, HIV vaccine efficacy may benefit from the induction of both humoral and cellular immune responses of maximal breadth, potency, and longevity. Guided by this rationale, we set out to develop an immunization protocol aimed at maximizing the induction of anti-Envelope (anti-Env) antibodies and CD8 + T cells targeting non-Env epitopes in rhesus macaques (RMs). Our approach was to deliver the entire simian immunodeficiency virus (SIV) proteome by serial vaccinations. To that end, 12 RMs were vaccinated over 81 weeks with DNA, modified vaccinia Ankara (MVA), vesicular stomatitis virus (VSV), adenovirus type 5 (Ad5), rhesus monkey rhadinovirus (RRV), and DNA again. Both the RRV and the final DNA boosters delivered a near-full-length SIVmac239 genome capable of assembling noninfectious SIV particles and inducing T-cell responses against all nine SIV proteins. Compared to previous SIV vaccine trials, the present DNA-MVA-VSV-Ad5-RRV-DNA regimen resulted in comparable levels of Env-binding antibodies and SIV-specific CD8 + T-cells. Interestingly, one vaccinee developed low titers of neutralizing antibodies (NAbs) against SIVmac239, a tier 3 virus. Following repeated intrarectal marginal-dose challenges with SIVmac239, vaccinees were not protected from SIV acquisition but manifested partial control of viremia. Strikingly, the animal with the low-titer vaccine-induced anti-SIVmac239 NAb response acquired infection after the first SIVmac239 exposure. Collectively, these results highlight the difficulties in eliciting protective immunity against immunodeficiency virus infection. IMPORTANCE Our results are relevant to HIV vaccine development efforts because they suggest that increasing the number of booster immunizations or delivering additional viral antigens may not necessarily improve vaccine efficacy against immunodeficiency virus infection.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.00979-20

Language: English

Publisher: American Society for Microbiology

Publication Date: 2020

detail.hit.zdb_id: 1495529-5

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Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys

Magnani, Diogo M. ; Ricciardi, Michael J. ; Bailey, Varian K. ; [et al.]

Elsevier BV ; 2017

In: Molecular Therapy Vol. 25, No. 10 ( 2017-10), p. 2323-2331

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In: Molecular Therapy, Elsevier BV, Vol. 25, No. 10 ( 2017-10), p. 2323-2331

Type of Medium: Online Resource

ISSN: 1525-0016

URL: Article

DOI: 10.1016/j.ymthe.2017.06.020

Language: English

Publisher: Elsevier BV

Publication Date: 2017

detail.hit.zdb_id: 2001818-6

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Vaccine protection against rectal acquisition of SIVmac239 in rhesus macaques

Gonzalez-Nieto, Lucas ; Castro, Isabelle M. ; Bischof, Georg F. ; [et al.]

Public Library of Science (PLoS) ; 2019

In: PLOS Pathogens Vol. 15, No. 9 ( 2019-9-30), p. e1008015-

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In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 15, No. 9 ( 2019-9-30), p. e1008015-

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1008015

DOI: 10.1371/journal.ppat.1008015.g001

DOI: 10.1371/journal.ppat.1008015.g002

DOI: 10.1371/journal.ppat.1008015.g003

DOI: 10.1371/journal.ppat.1008015.g004

DOI: 10.1371/journal.ppat.1008015.g005

DOI: 10.1371/journal.ppat.1008015.g006

DOI: 10.1371/journal.ppat.1008015.g007

DOI: 10.1371/journal.ppat.1008015.g008

DOI: 10.1371/journal.ppat.1008015.g009

DOI: 10.1371/journal.ppat.1008015.g010

DOI: 10.1371/journal.ppat.1008015.t001

DOI: 10.1371/journal.ppat.1008015.t002

DOI: 10.1371/journal.ppat.1008015.t003

DOI: 10.1371/journal.ppat.1008015.s001

DOI: 10.1371/journal.ppat.1008015.s002

DOI: 10.1371/journal.ppat.1008015.s003

DOI: 10.1371/journal.ppat.1008015.s004

DOI: 10.1371/journal.ppat.1008015.s005

DOI: 10.1371/journal.ppat.1008015.s006

DOI: 10.1371/journal.ppat.1008015.s007

DOI: 10.1371/journal.ppat.1008015.s008

DOI: 10.1371/journal.ppat.1008015.s009

DOI: 10.1371/journal.ppat.1008015.s010

DOI: 10.1371/journal.ppat.1008015.s011

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2019

detail.hit.zdb_id: 2205412-1

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Induction of Transient Virus Replication Facilitates Antigen-Independent Isolation of SIV-Specific Monoclonal Antibodies

Pedreño-Lopez, Nuria ; Dang, Christine M. ; Rosen, Brandon C. ; [et al.]

Elsevier BV ; 2020

In: Molecular Therapy - Methods & Clinical Development Vol. 16 ( 2020-03), p. 225-237

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In: Molecular Therapy - Methods & Clinical Development, Elsevier BV, Vol. 16 ( 2020-03), p. 225-237

Type of Medium: Online Resource

ISSN: 2329-0501

URL: Article

DOI: 10.1016/j.omtm.2020.01.010

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2863173-0

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Use of a Recombinant Gamma-2 Herpesvirus Vaccine Vector against Dengue Virus in Rhesus Monkeys

Bischof, Georg F. ; Magnani, Diogo M. ; Ricciardi, Michael ; [et al.]

American Society for Microbiology ; 2017

In: Journal of Virology Vol. 91, No. 16 ( 2017-08-15)

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In: Journal of Virology, American Society for Microbiology, Vol. 91, No. 16 ( 2017-08-15)

Abstract: Research on vaccine approaches that can provide long-term protection against dengue virus infection is needed. Here we describe the construction, immunogenicity, and preliminary information on the protective capacity of recombinant, replication-competent rhesus monkey rhadinovirus (RRV), a persisting herpesvirus. One RRV construct expressed nonstructural protein 5 (NS5), while a second recombinant expressed a soluble variant of the E protein (E85) of dengue virus 2 (DENV2). Four rhesus macaques received a single vaccination with a mixture of both recombinant RRVs and were subsequently challenged 19 weeks later with 1 × 10 5 PFU of DENV2. During the vaccine phase, plasma of all vaccinated monkeys showed neutralizing activity against DENV2. Cellular immune responses against NS5 were also elicited, as evidenced by major histocompatibility complex class I (MHC-I) tetramer staining in the one vaccinated monkey that was Mamu-A*01 positive. Unlike two of two unvaccinated controls, two of the four vaccinated monkeys showed no detectable viral RNA sequences in plasma after challenge. One of these two monkeys also showed no anamnestic increases in antibody levels following challenge and thus appeared to be protected against the acquisition of DENV2 following high-dose challenge. Continued study will be needed to evaluate the performance of herpesviral and other persisting vectors for achieving long-term protection against dengue virus infection. IMPORTANCE Continuing studies of vaccine approaches against dengue virus (DENV) infection are warranted, particularly ones that may provide long-term immunity against all four serotypes. Here we investigated whether recombinant rhesus monkey rhadinovirus (RRV) could be used as a vaccine against DENV2 infection in rhesus monkeys. Upon vaccination, all animals generated antibodies capable of neutralizing DENV2. Two of four vaccinated monkeys showed no detectable viral RNA after subsequent high-dose DENV2 challenge at 19 weeks postvaccination. Furthermore, one of these vaccinated monkeys appeared to be protected against the acquisition of DENV2 infection on the basis of undetectable viral loads and the lack of an anamnestic antibody response. These findings underscore the potential utility of recombinant herpesviruses as vaccine vectors.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.00525-17

Language: English

Publisher: American Society for Microbiology

Publication Date: 2017

detail.hit.zdb_id: 1495529-5

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A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus

Magnani, Diogo M. ; Silveira, Cassia G. T. ; Rosen, Brandon C. ; [et al.]

Public Library of Science (PLoS) ; 2017

In: PLOS Neglected Tropical Diseases Vol. 11, No. 6 ( 2017-6-12), p. e0005655-

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In: PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 11, No. 6 ( 2017-6-12), p. e0005655-

Type of Medium: Online Resource

ISSN: 1935-2735

URL: Article

DOI: 10.1371/journal.pntd.0005655

DOI: 10.1371/journal.pntd.0005655.g001

DOI: 10.1371/journal.pntd.0005655.g002

DOI: 10.1371/journal.pntd.0005655.g003

DOI: 10.1371/journal.pntd.0005655.g004

DOI: 10.1371/journal.pntd.0005655.g005

DOI: 10.1371/journal.pntd.0005655.t001

DOI: 10.1371/journal.pntd.0005655.s001

DOI: 10.1371/journal.pntd.0005655.s002

DOI: 10.1371/journal.pntd.0005655.s003

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2017

detail.hit.zdb_id: 2429704-5

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