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BACKGROUND: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants. METHODS: In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18-60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1:1:1:1) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination. FINDINGS: All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12-36] vs 28% [five of 18 participants, 10-54]), and erythema (13% [seven of 54 participants, 5-25] vs 39% [seven of 18 participants, 17-64]), with headache (32% [17 of 54 participants, 20-46] vs 44% [eight of 18 participants, 22-69]) and malaise (26% [14 of 54 participants, 15-40] vs 33% [six of 18 participants, 13-59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82-100), 89% (16 participants, 65-99), 100% (18 participants, 82-100), and 94% (17 participants, 73-100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID50 groups, and YF-VAX group, respectively, remained seroprotected through D180. INTERPRETATION: vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development. FUNDING: Sanofi.
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BACKGROUND: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial. METHODS: In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 µg or 50 µg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181. Enrolment and randomisation occurred sequentially by group; randomisation was done by an interactive web-based randomisation system and only designated unmasked study personnel had access to the randomisation code. Adults were required to be seronegative and unvaccinated for inclusion. Local and systemic reactogenicity, adverse events, binding and neutralising antibodies, and antigen-specific T-cell responses were quantified. For safety analyses, exact 95% Clopper-Pearson CIs for the probability of any incidence of an unsolicited adverse event was computed for each group. For immunogenicity results, CIs for binary variables were computed using the exact Clopper-Pearson methodology, while CIs for geometric mean titres were based on 10 000 empirical bootstrap samples. Post-hoc, paired one-sample t tests were used to assess the increase in mean log-10 neutralising antibody titres between day 29 and day 43 (after the second vaccination) for the primary SARS-CoV-2 targets of interest. This trial is registered at ClinicalTrials.gov, NCT04784767, and is closed to new participants. FINDINGS: Between April 7, and June 29, 2021, 29 participants were enrolled in the study. 20 individuals were assigned to receive 25 µg SpFN/ALFQ, four to 50 µg SpFN/ALFQ, and five to placebo. Neutralising antibody responses peaked at day 43, 2 weeks after the second dose. Neutralisation activity against multiple omicron subvariants decayed more slowly than against the D614G or beta variants until 5 months after second vaccination for both dose groups. CD4+ T-cell responses were elicited 4 weeks after the first dose and were boosted after a second dose of SpFN/ALFQ for both dose groups. Neutralising antibody titres against early omicron subvariants and clade 1 sarbecoviruses were detectable after two immunisations and peaked after the third immunisation for both dose groups. Neutralising antibody titres against XBB.1.5 were detected after three vaccinations. Passive IgG transfer from vaccinated volunteers into Syrian golden hamsters controlled replication of SARS-CoV-1 after challenge. INTERPRETATION: SpFN/ALFQ was well tolerated and elicited robust and durable binding antibody and neutralising antibody titres against a broad panel of SARS-CoV-2 variants and other sarbecoviruses. FUNDING: US Department of Defense, Defense Health Agency.
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Vacinas contra COVID-19 , COVID-19 , Ferritinas , Lipídeo A , Lipossomos , Nanopartículas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Adulto , Masculino , Feminino , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Nanopartículas/administração & dosagem , Lipídeo A/análogos & derivados , Lipídeo A/administração & dosagem , Lipídeo A/farmacologia , Lipídeo A/imunologia , Lipossomos/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia , Saponinas/administração & dosagem , Saponinas/imunologia , Saponinas/farmacologia , Saponinas/efeitos adversos , Anticorpos Antivirais/sangue , Pessoa de Meia-Idade , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Adjuvantes de Vacinas/administração & dosagem , Anticorpos Neutralizantes/sangue , Adulto Jovem , NanovacinasRESUMO
BACKGROUND: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control. METHODS: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Among 231 (70%) participants, most were male (184/80%), and from Jordan (217/94%). Among 188 treatment-experienced-participants (>6 months), 165 (88%) were virally suppressed. High-level resistance was most frequent against nucleoside reverse transcriptase inhibitor (13/81%), and integrase-strand transfer inhibitor (INSTI) (10/62%) drugs among viremic (≥1000 HIV copies/mL) treatment-experienced participants with drug-resistant mutations (DRMs, n = 16). Common HIV subtypes (n = 43) were B (6/14%), A1 (5/12%), and CRF01_AE (5/12%); additionally, novel recombinant forms were detected. In multivariate analysis, independently higher risk for late diagnosis (n = 49) was observed with diagnosis through blood donation (vs check-up: RR 2.20, 95%CI 1.16-4.17) and earlier time-period of diagnosis (1986-2014 vs 2015-2021: RR 2.87, 95%CI 1.46-5.62). CONCLUSIONS: Late diagnosis and INSTI resistance endanger national HIV prevention and treatment in Jordan-high-level resistance to INSTI suggests therapeutic drug monitoring is needed for treatment efficacy and conservation of treatment options.
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Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , Carga Viral , Humanos , Jordânia/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Infecções por HIV/tratamento farmacológico , Masculino , Adulto , Feminino , Estudos Transversais , Farmacorresistência Viral/genética , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adulto Jovem , Genótipo , AdolescenteRESUMO
Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2â g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.
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Febre Lassa , Vírus Lassa , Humanos , Animais , Bovinos , Cães , Suínos , Vírus Lassa/genética , Febre Lassa/epidemiologia , Febre Lassa/veterinária , Febre Lassa/genética , Nigéria/epidemiologia , Genoma Viral , Saúde Pública , MamíferosRESUMO
BACKGROUND: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults. METHODS: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1â×â1010 or 1â×â1011 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056. FINDINGS: Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1â×â1010 pu (n=20) or 1â×â1011 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1â×â1010 pu group and 545 [276-1078] in the 1â×â1011 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1â×1010 pu group and 27 [95-156] in the 1â×1011 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination. INTERPRETATION: This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions. FUNDING: National Institutes of Health.
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Adenovirus dos Símios , Marburgvirus , Animais , Adulto , Humanos , Pan troglodytes , Anticorpos Antivirais , Vacinas Sintéticas/efeitos adversos , Adenoviridae , Glicoproteínas , Método Duplo-CegoRESUMO
BACKGROUND: Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected. METHODS: Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed. RESULTS: Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL <3.09 (sensitivity and specificity 96%) at entry into isolation were likely SARS-CoV-2 uninfected. Viral load >4.58 log10 RNA copies/mL or anti-SARS-CoV-2 signal-to-cutoff ratio <1.38 (VL: sensitivity and specificity 93%; anti-SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected. CONCLUSIONS: Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Teste para COVID-19 , Sensibilidade e Especificidade , RNA , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Significant variability exists in the application of infection control policy throughout the US Army initial entry training environment. To generate actionable information for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) transmission among new recruits, active enhanced surveillance was conducted for evidence of and exposure to SARS-CoV-2/COVID-19. METHODS: We serially tested recruits with a reverse transcriptase polymerase chain reaction (RT-PCR) COVID-19 and/or total antibody to SARS-CoV-2 tests at days 0, 14, and week 10 upon arrival for basic combat training at a location in the Southern United States. RESULTS: Among 1403 recruits who were enrolled over a 6-week period from August 25 through October 11, 2020, 84 recruits tested positive by RT-PCR, with more than half (55%, 46/84) testing positive at arrival and almost two-thirds (63%, 53/84) also testing seropositive at arrival. Similarly, among an overall 146 recruits who tested seropositive for SARS-CoV-2 during the period of observation, a majority (86%) tested seropositive at arrival; no hospitalizations were observed among seropositive recruits, and antibody response increased at week 10. CONCLUSIONS: These findings that suggest serological testing may complement current test-based measures and provide another tool to incorporate in COVID-19 mitigation measures among trainees in the US Army.
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Zika virus (ZIKV) and dengue virus (DENV) are antigenically related mosquito-borne flaviviruses. ZIKV is becoming increasingly prevalent in DENV-endemic regions, raising the possibility that pre-existing immunity to one virus could modulate the response to a heterologous virus, although whether this would be beneficial or detrimental is unclear. Here, we analyzed sera from residents of a DENV-endemic region of Thailand to determine the prevalence of DENV-elicited antibodies capable of cross-neutralizing ZIKV. Sixty-one participants who were asymptomatic and unselected for viral serostatus were enrolled. Among them, 52 and 51 were seropositive for IgG antibody against DENV or ZIKV E proteins (ELISA assay), respectively. Notably, 44.23% (23/52) of DENV seropositive participants had serological evidence of multiple exposures to DENV, and these subjects had strikingly higher titers and broader reactivities of neutralizing antibodies (NAbs) against ZIKV and DENV heterotypes compared with participants with serological evidence of a single DENV infection (25/52, 48.1%). In total, 17 of the 61 participants (27.9%) had NAbs against ZIKV and all four DENV serotypes, and an additional 9 (14.8%) had NAbs against ZIKV and DENV1, 2, and 3. NAbs against DENV2 were the most prevalent (44/61, 72.1%) followed by DENV3 (38/61, 62.3%) and DENV1 (36/61, 59.0%). Of note, anti-ZIKV NAbs were more prevalent than anti-DENV4 NAbs (27/61, 44.3% and 21/61, 34.4%, respectively). Primary ZIKV infection was detected in two participants, confirming that ZIKV co-circulates in this region. Thus, residents of DENV-endemic regions with repeated exposure to DENV have higher titers of NAbs against ZIKV than individuals with only a single DENV exposure.
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Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , Vírus da Dengue/imunologia , Zika virus/imunologia , Adolescente , Adulto , Idoso , Dengue/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tailândia , Adulto Jovem , Infecção por Zika virus/virologiaRESUMO
Dengue virus (DENV) is the cause of one of the most prevalent neglected tropical diseases, and up to half of the world's population is at risk for infection. Recent results from clinical trials have shown that DENV vaccination can induce the development of severe dengue disease and/or prolong hospitalization after natural infection in certain naive populations. Thus, it is crucial that vaccine development takes into account the history of DENV exposure in the targeted population. In Nepal, DENV infection was first documented in 2004, and despite the increasing prevalence of DENV infection, the population remains relatively naive. However, it is not known which of the four DENV serotypes circulate in Nepal or whether there is evidence of repeated exposure to DENV in the Nepali population. To address this, we studied 112 patients who presented with symptomology suspicious for DENV infection at clinics throughout Nepal during late 2015 and early 2016. Of the 112 patients examined, 39 showed serological and/or genetic evidence of primary or secondary DENV infection: 30 were positive for DENV exposure by IgM/IgG ELISA, two by real-time reverse-transcription PCR (RT-PCR), and seven by both methods. Dengue virus 1-3, but not DENV4, serotypes were detected by RT-PCR. Whole genome sequencing of two DENV2 strains isolated from patients with primary and secondary infections suggests that DENV was introduced into Nepal through India, with which it shares a porous border. Further study is needed to better define the DENV epidemic in Nepal, a country with limited scientific resources and infrastructure.
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Vírus da Dengue/classificação , Dengue/epidemiologia , Dengue/virologia , Genoma Viral/genética , Sequenciamento Completo do Genoma , Adolescente , Adulto , Idoso , Criança , Surtos de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Filogenia , Sorogrupo , Adulto JovemRESUMO
Universal HIV and HCV screening in emergency departments (ED) can reach populations who are less likely to get tested otherwise. The objective of this analysis was to evaluate universal opt-out HIV and HCV screening in two EDs in San Diego. HIV screening for persons aged 13-64 years (excluding persons known to be HIV+ or reporting HIV testing within last 12 months) was implemented using a 4th generation HIV antigen/antibody assay; HCV screening was offered to persons born between 1945 and 1965. Over a period of 16 months, 12,575 individuals were tested for HIV, resulting in 33 (0.26%) new HIV diagnoses, of whom 30 (90%) were successfully linked to care. Universal screening also identified 74 out-of-care for >12-months HIV+ individuals of whom 50 (68%) were successfully relinked to care. Over a one-month period, HCV antibody tests were conducted in 905 individuals with a seropositivity rate of 9.9% (90/905); 61 seropositives who were newly identified or never treated for HCV had HCV RNA testing, of which 31 (51%) resulted positive (3.4% of all participants, including 18 newly identified RNA positives representing 2% of all participants), and 13/31 individuals (42%) were linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by >7-fold, underlining the importance of HCV screening in EDs.
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Serviço Hospitalar de Emergência , Infecções por HIV/diagnóstico , Hepatite C/diagnóstico , Programas de Rastreamento/métodos , Sorodiagnóstico da AIDS , Adolescente , Adulto , Idoso , Algoritmos , California/epidemiologia , Estudos de Coortes , Infecções por HIV/epidemiologia , Soroprevalência de HIV , Hepatite C/epidemiologia , Humanos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Antibody (Ab)-dependent enhancement can exacerbate dengue virus (DENV) infection due to cross-reactive Abs from an initial DENV infection, facilitating replication of a second DENV. Zika virus (ZIKV) emerged in DENV-endemic areas, raising questions about whether existing immunity could affect these related flaviviruses. We show that mice born with circulating maternal Abs against ZIKV develop severe disease upon DENV infection. Compared with pups of naive mothers, those born to ZIKV-immune mice lacking type I interferon receptor in myeloid cells (LysMCre+Ifnar1fl/fl) exhibit heightened disease and viremia upon DENV infection. Passive transfer of IgG isolated from mice born to ZIKV-immune mothers resulted in increased viremia in naive recipient mice. Treatment with Abs blocking inflammatory cytokine tumor necrosis factor linked to DENV disease or Abs blocking DENV entry improved survival of DENV-infected mice born to ZIKV-immune mothers. Thus, the maternal Ab response to ZIKV infection or vaccination might predispose to severe dengue disease in infants.
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Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , Linhagem Celular , Reações Cruzadas/imunologia , Culicidae , Citocinas/metabolismo , Vírus da Dengue/patogenicidade , Modelos Animais de Doenças , Feminino , Humanos , Imunidade , Imunoglobulina G , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides , Receptor de Interferon alfa e beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Viremia , Internalização do Vírus , Zika virus/patogenicidade , Infecção por Zika virus/virologiaRESUMO
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus linked to devastating neurologic diseases. Immune responses to flaviviruses may be pathogenic or protective. Our understanding of human immune responses to ZIKV in vivo remains limited. Therefore, we performed a longitudinal molecular and phenotypic characterization of innate and adaptive immune responses during an acute ZIKV infection. We found that innate immune transcriptional and genomic responses were both cell type- and time-dependent. While interferon stimulated gene induction was common to all innate immune cells, the upregulation of important inflammatory cytokine genes was primarily limited to monocyte subsets. Additionally, genomic analysis revealed substantial chromatin remodeling at sites containing cell-type specific transcription factor binding motifs that may explain the observed changes in gene expression. In this dengue virus-experienced individual, adaptive immune responses were rapidly mobilized with T cell transcriptional activity and ZIKV neutralizing antibody responses peaking 6 days after the onset of symptoms. Collectively this study characterizes the development and resolution of an in vivo human immune response to acute ZIKV infection in an individual with pre-existing flavivirus immunity.
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Infecção por Zika virus/imunologia , Zika virus/imunologia , Doença Aguda , Imunidade Adaptativa , Adulto , Anticorpos Antivirais/imunologia , Cromatina/genética , Cromatina/imunologia , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Estudos Longitudinais , Filogenia , Linfócitos T/imunologia , Viagem , Venezuela , Zika virus/classificação , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/genética , Infecção por Zika virus/virologiaRESUMO
Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.