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1.
Pediatrics ; 148(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34493538

RESUMO

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of the influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2021-2022 season. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during circulation of severe acute respiratory syndrome coronavirus 2, which is expected to continue during this influenza season. In this technical report, we summarize recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, vaccination coverage, and detailed guidance on storage, administration, and implementation. We also provide background on inactivated and live attenuated influenza vaccine recommendations, vaccination during pregnancy and breastfeeding, diagnostic testing, and antiviral medications for treatment and chemoprophylaxis.


Assuntos
Vacinas contra Influenza , Influenza Humana/prevenção & controle , Antivirais/uso terapêutico , Aleitamento Materno , Criança , Contraindicações de Medicamentos , Farmacorresistência Viral , Armazenamento de Medicamentos , Feminino , Hospitalização , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/mortalidade , Vacinação em Massa , Fatores de Risco , Estados Unidos/epidemiologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos
2.
Nat Med ; 27(9): 1636-1645, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34518679

RESUMO

The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 105, 9.0 × 105 or 1.8 × 106 PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 105 dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2+Vγ9+ T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2+Vγ9+ T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.


Assuntos
Vacinas Antimaláricas/administração & dosagem , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Vacinas Atenuadas/administração & dosagem , Adulto , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Método Duplo-Cego , Humanos , Lactente , Quênia/epidemiologia , Vacinas Antimaláricas/efeitos adversos , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/patogenicidade , Esporozoítos/efeitos dos fármacos , Esporozoítos/patogenicidade , Linfócitos T/efeitos dos fármacos , Vacinação , Vacinas Atenuadas/efeitos adversos
3.
Vaccine ; 39(43): 6378-6384, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34561139

RESUMO

IMPORTANCE: Passive surveillance systems are susceptible to the under-reporting of adverse events (AE) and a lack of information pertaining to vaccinated populations. Conventional active surveillance focuses on predefined AEs. Advanced data mining tools could be used to identify unusual clusters of potential AEs after vaccination. OBJECTIVE: To assess the feasibility of a novel tree-based statistical approach to the identification of AE clustering following the implementation of a varicella vaccination program among one-year-olds. SETTING AND PARTICIPANTS: This nationwide safety surveillance was based on data from the Taiwan National Health Insurance database and National Immunization Information System for the period 2004 through 2014. The study population was children aged 12-35 months who received the varicella vaccine. EXPOSURE: First-dose varicella vaccine. OUTCOMES AND MEASURES: All incident ICD-9-CM diagnoses (emergency or inpatient departments) occurring 1-56 days after the varicella vaccination were classified within a hierarchical system of diagnosis categories using Multi-Level Clinical Classifications Software. A self-controlled tree-temporal data mining tool was then used to explore the incidence of AE clustering with a variety of potential risk intervals. The comparison interval consisted of days in the 56-day follow-up period that fell outside the risk interval. RESULTS: Among 1,194,189 varicella vaccinees with no other same-day vaccinations, nine diagnoses with clustering features were categorized into four safety signals: fever on days 1-6 (attributable risk [AR] 38.5 per 100,000, p < 0.001), gastritis and duodenitis on days 1-2 (AR 5.9 per 100,000, p < 0.001), acute upper respiratory infection on days 1-5 (AR 11.0 per 100,000, p = 0.006), and varicella infection on days 1-9 (AR 2.7 per 100,000, p < 0.001). These safety profiles and their corresponding risk intervals have been identified in previous safety surveillance studies. CONCLUSIONS: Unexpected clusters of AEs were not detected after the mass administration of childhood varicella vaccines in Taiwan. The tree-temporal statistical method is a feasible approach to the safety surveillance of vaccines in populations of young children.


Assuntos
Vacina contra Varicela , Varicela , Varicela/epidemiologia , Varicela/prevenção & controle , Vacina contra Varicela/efeitos adversos , Pré-Escolar , Humanos , Programas de Imunização , Lactente , Vacinação/efeitos adversos , Vacinas Atenuadas/efeitos adversos
4.
Front Immunol ; 12: 667889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512622

RESUMO

Type 1 diabetes (T1D) is the most common paediatric endocrine disease, and its frequency has been found to increase worldwide. Similar to all conditions associated with poorly regulated glucose metabolism, T1D carries an increased risk of infection. Consequently, careful compliance by T1D children with schedules officially approved for child immunization is strongly recommended. However, because patients with T1D show persistent and profound limitations in immune function, vaccines may evoke a less efficient immune response, with corresponding lower protection. Moreover, T1D is an autoimmune condition that develops in genetically susceptible individuals and some data regarding T1D triggering factors appear to indicate that infections, mainly those due to viruses, play a major role. Accordingly, the use of viral live attenuated vaccines is being debated. In this narrative review, we discussed the most effective and safe use of vaccines in patients at risk of or with overt T1D. Literature analysis showed that several problems related to the use of vaccines in children with T1D have not been completely resolved. There are few studies regarding the immunogenicity and efficacy of vaccines in T1D children, and the need for different immunization schedules has not been precisely established. Fortunately, the previous presumed relationship between vaccine administration and T1D appears to have been debunked, though some doubts regarding rotavirus vaccines remain. Further studies are needed to completely resolve the problems related to vaccine administration in T1D patients. In the meantime, the use of vaccines remains extensively recommended in children with this disease.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Vacinação , Vacinas Virais/administração & dosagem , Viroses/prevenção & controle , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Medição de Risco , Fatores de Risco , Vacinação/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos , Viroses/epidemiologia , Viroses/imunologia , Viroses/virologia
5.
PLoS One ; 16(8): e0255720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34358275

RESUMO

Mozambique introduced the monovalent rotavirus vaccine (Rotarix®, GSK Biologicals, Rixensart, Belgium) in September 2015. Previous analysis, showed that Nampula province continues reporting a high frequency of Rotavirus A (RVA) infection and the emergence of G9P[6], G9P[4] and G3P[4] genotypes. This analysis aimed to determine the RVA frequency; risk factors; genotype distribution by vaccination status and age between pre- and post-vaccine periods in children under-five years old with diarrhea in Nampula. A cross-sectional, hospital-based surveillance study was conducted in the Hospital Central de Nampula in Mozambique. Socio-demographic and clinical data were collected to assess factors related to RVA infection in both periods. Stool specimens were screened to detect RVA by ELISA, and positive samples were genotyped. Between 2015 (pre-vaccine period) and 2016-2019 (post-vaccine period), 614 stool specimens were collected and tested for RVA in which 34.9% (67/192) were positive in pre-vaccine period and 21.8% (92/422) in post-vaccine (p = 0.001). In the post-vaccine period, age, year, and contact with different animal species (chicken, duck, or multiple animals) were associated with RVA infection. RVA infection was higher in children partially vaccinated (40.7%, 11/27) followed by the fully vaccinated (29.3%, 56/191) and the unvaccinated (15.3%, 21/137) (p = 0.002). G1P[8] and G9P[4] were common in vaccinated children less than 12 months. The present analysis showed that RVA infection reduced slightly in the post-vaccine period, with a high proportion of infection and genotype diversity in children, under 12 months of age, vaccinated. Further research on factors associated with RVA infection on vaccinated compared to unvaccinated children and vaccination optimization should be done.


Assuntos
Diarreia/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/genética , Animais , Pré-Escolar , Diarreia/epidemiologia , Diarreia/genética , Diarreia/virologia , Fezes/virologia , Feminino , Genótipo , Humanos , Lactente , Masculino , Fatores de Risco , Rotavirus/efeitos dos fármacos , Rotavirus/patogenicidade , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/genética , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/efeitos adversos , Vacinação , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos
6.
Nature ; 595(7866): 289-294, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34194041

RESUMO

The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))-which kill liver-stage and blood-stage parasites, respectively-and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization ( https://clinicaltrials.gov/ , NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.


Assuntos
Anticorpos Neutralizantes/imunologia , Fígado/imunologia , Fígado/parasitologia , Vacinas Antimaláricas/imunologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Vacinas Atenuadas/imunologia , Adulto , Animais , Formação de Anticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estágios do Ciclo de Vida/imunologia , Malária/sangue , Malária/imunologia , Malária/parasitologia , Malária/prevenção & controle , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/química , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/crescimento & desenvolvimento , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Vacinação/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/química
7.
Vaccine ; 39(32): 4463-4470, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34218961

RESUMO

BACKGROUND AND AIMS: ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated G1P8 (KH0118) strain by Center for Research and Production of Vaccines and Biologicals (POLYVAC), Vietnam. This study compared the safety and immunogenicity of these two formulations. METHODS: A Phase 3, randomized, partially double-blinded, active-controlled study was conducted in healthy infants aged 60-91 days in Vietnam. Infants received two doses of ROTAVIN or ROTAVIN-M1 in a ratio of 2:1 with an interval of 8 weeks. Solicited reactions were collected for 7 days after each vaccination. Blood samples were collected pre-vaccination and 4 weeks after the second vaccination in a subset of infants. Non-inferiority criteria required that the lower bound of 95% confidence intervals (CIs) of the post-vaccination anti-rotavirus IgA GMC (Geometric Mean Concentration) ratio of ROTAVIN/ROTAVIN-M1 should be >0.5. A co-primary objective was to compare the safety of the two vaccines in terms of solicited reactions. RESULTS: A total of 825 infants were enrolled. The post-vaccination GMC was 48.25 (95% CI: 40.59, 57.37) in the ROTAVIN group and 35.04 (95% CI: 27.34, 44.91) in the ROTAVIN-M1 group with an IgA GMC ratio of 1.38 (95% CI: 1.02, 1.86) thus meeting the pre-set criteria for non-inferiority. A total of 605 solicited reactions were reported in 297 (36.0%) participants with 35.4% in the ROTAVIN group and 37.2% in the ROTAVIN-M1 group. There were no cases of intussusception or death reported in the study. CONCLUSIONS: Based on the data generated, it can be concluded that ROTAVIN is immunologically non-inferior and has similar safety profile to ROTAVIN-M1 when administered to infants in a two-dose schedule. Therefore, it can be considered as a more suitable option for programmatic use to prevent rotavirus diarrhoea in Vietnam and the Mekong region. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03703336, October 11, 2018.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Anticorpos Antivirais , Grupo com Ancestrais do Continente Asiático , Humanos , Imunogenicidade da Vacina , Lactente , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Vietnã
8.
Vaccine ; 39(33): 4651-4658, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34244006

RESUMO

BACKGROUND: Despite safe and effective WHO prequalified rotavirus vaccines, at least 84 million children remain unvaccinated. A birth dose schedule of the RV3-BB vaccine was reported to be highly efficacious against severe rotavirus disease in Indonesian infants and is under further development at PT Bio Farma, Indonesia. The aim is to develop a rotavirus vaccine starting from birth that could improve the implementation, safety, and effectiveness of vaccines. METHODS: A multi-site phase I study of a human neonatal RV3 rotavirus vaccine (Bio Farma) in adults, children, neonates in Indonesia from April 2018 to March 2019. The adult and child cohorts were open-labeled single-dose, while the neonatal cohort was randomized, double-blind, and placebo-controlled three-doses at the age of 0-5 days, 8-10 weeks, and 12-14 weeks. The primary objective was to assess the safety of vaccines with the immunogenicity and vaccine virus fecal shedding as the secondary endpoints in neonates. RESULTS: Twenty-five adults, 25 children, and 50 neonates were recruited, and all but one in the neonatal cohort completed all study procedures. Three serious adverse events were reported (1 adult & 2 neonates), but none were assessed related to investigational product (IP). The neonatal vaccine group had a significantly higher positive immune response (cumulative seroconverted SNA and IgA) 28 days after three doses than those in the placebo group (72% vs. 16.7%, respectively). The GMT of serum IgA in the vaccine group was significantly higher at post IP dose 1 (p < 0.05) and post IP dose 3 (p < 0.001) compared to the placebo group. CONCLUSION: The trial results show that the RV3 rotavirus vaccine (Bio Farma) is well tolerated in all participant cohorts (adults, children, and neonates). Three doses of this vaccine administered in a neonatal schedule were immunogenic. These promising results support further clinical development of the RV3 rotavirus vaccine (Bio Farma).


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Adulto , Anticorpos Antivirais , Criança , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Indonésia , Lactente , Recém-Nascido , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas Atenuadas/efeitos adversos
9.
Vaccine ; 39(32): 4429-4436, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34175128

RESUMO

INTRODUCTION: Annually more than 100,000 Japanese encephalitis (JE) cases and 25,000 deaths worldwide are caused by JE virus infection. More than 15 JE vaccines are currently in use worldwide. It is unknown whether any of the vaccines is superior to the others in terms of immunogenicity and safety. METHODS: Four databases were systematically searched for randomised controlled trials that compared two or more types of JE vaccines. Vaccines were classified into four classes: inactivated mouse brain-derived (oldest class), inactivated Vero cell, live chimeric, and live attenuated. Network meta-analysis was used to generate mixed effect estimates against inactivated mouse brain-derived vaccines for seroconversion, and against placebo for adverse event (AE) and severe adverse event (SAE). RESULTS: 23 studies (38,496 participants) were included. All newer vaccine classes had better immunogenicity, the difference was statistically significant for inactivated Vero cell (OR = 2.98; 95 %CI: 1.02-8.65) and live chimeric (OR = 5.93; 95 %CI: 1.73-20.32) vaccines. Inactivated mouse-derived vaccines had the highest odds for AEs (OR = 2.27; 95 %CI: 1.59-3.23), the odds of AE of newer vaccines was not different to placebo. There was no difference in SAEs across vaccine classes. CONCLUSIONS: All newer JE vaccines have comparable safety profiles, live chimeric and inactivated Vero cell vaccines are the most immunogenic among the newer vaccine classes.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Vacinas contra Encefalite Japonesa , Animais , Anticorpos Antivirais , Encefalite Japonesa/prevenção & controle , Vacinas contra Encefalite Japonesa/efeitos adversos , Camundongos , Metanálise em Rede , Vacinação , Vacinas Atenuadas/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos
10.
Vaccine ; 39(25): 3338-3345, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33992440

RESUMO

BACKGROUND AND OBJECTIVE: Vaccination with the live attenuated measles vaccine is currently recommended two years after hematopoietic stem cell transplantation (HSCT) and generally contraindicated after solid organ transplantation (SOT) due to safety concerns. However, in the last few years new data on the administration of the measles vaccine to HSCT recipients less two years post-transplantation and to SOT recipients have become available. This new data may change current guidelines and practices. The objective of this review is to provide an overview of the current data on the safety and efficacy of early measles vaccination for HSCT- and SOT recipients. METHOD: PubMed and EMBASE were searched from the earliest date available through October 2019 to identify all research that reported on the safety and efficacy of measles vaccination after SOT or less than two years after HSCT. RESULTS: A total of ten studies was included in this review. In the six studies that evaluated the efficacy of measles vaccination after SOT, seroconversion rates ranged from 41 to 100% after one dose and 73 to 100% after two doses. In the four studies that evaluated the efficacy of measles vaccination less than two years after HSCT, seroconversion rates ranged from 33 to 100% after one dose and 100% after two doses. In all studies, the administration of the measles vaccine after transplantation was considered to be safe. There were no cases of infection with the attenuated vaccine strain, and there were no adverse events related to the vaccination. CONCLUSION: Data on the administration of the measles vaccine after SOT and less than two years after HSCT is scarce. However, the current data available suggest that it is efficacious and well tolerable. Therefore, early measles vaccination could be considered in selected groups of SOT- and HSCT recipients during increased measles transmission or an outbreak setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vacina contra Sarampo , Transplantados , Vacinação , Vacinas Atenuadas/efeitos adversos
11.
Nat Commun ; 12(1): 2518, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947856

RESUMO

Immunization with Plasmodium falciparum (Pf) sporozoites under chemoprophylaxis (PfSPZ-CVac) is the most efficacious approach to malaria vaccination. Implementation is hampered by a complex chemoprophylaxis regimen and missing evidence for efficacy against heterologous infection. We report the results of a double-blinded, randomized, placebo-controlled trial of a simplified, condensed immunization regimen in malaria-naive volunteers (EudraCT-Nr: 2018-004523-36). Participants are immunized by direct venous inoculation of 1.1 × 105 aseptic, purified, cryopreserved PfSPZ (PfSPZ Challenge) of the PfNF54 strain or normal saline (placebo) on days 1, 6 and 29, with simultaneous oral administration of 10 mg/kg chloroquine base. Primary endpoints are vaccine efficacy tested by controlled human malaria infection (CHMI) using the highly divergent, heterologous strain Pf7G8 and safety. Twelve weeks following immunization, 10/13 participants in the vaccine group are sterilely protected against heterologous CHMI, while (5/5) participants receiving placebo develop parasitemia (risk difference: 77%, p = 0.004, Boschloo's test). Immunization is well tolerated with self-limiting grade 1-2 headaches, pyrexia and fatigue that diminish with each vaccination. Immunization induces 18-fold higher anti-Pf circumsporozoite protein (PfCSP) antibody levels in protected than in unprotected vaccinees (p = 0.028). In addition anti-PfMSP2 antibodies are strongly protection-associated by protein microarray assessment. This PfSPZ-CVac regimen is highly efficacious, simple, safe, well tolerated and highly immunogenic.


Assuntos
Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Vacinação/métodos , Vacinas Atenuadas/imunologia , Adulto , Antimaláricos/uso terapêutico , Linhagem Celular , Quimioprevenção , Cloroquina/uso terapêutico , Feminino , Humanos , Imunoglobulina G/imunologia , Vacinas Antimaláricas/efeitos adversos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Masculino , Parasitemia/imunologia , Análise Serial de Proteínas , Esporozoítos/imunologia , Vacinação/efeitos adversos , Vacinas Atenuadas/efeitos adversos
12.
Virus Genes ; 57(3): 266-275, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33950332

RESUMO

An outbreak of canine distemper in 2017 in mink breeding farms (Shandong province, China) caused severe pneumonia, hardened footpads, and death in more than 5000 vaccinated animals. Sequencing of the hemagglutinin and fusion protein genes from the WH2 canine distemper virus (CDV) strain we isolated from the infected minks were clustered into the recently isolated CDV Asia-1 genotype group. The WH2 strain was distinct from the current vaccine strains, containing a novel potential N-glycosylation site in its hemagglutinin protein. It also contained amino acid mutations in the fusion protein gene (I87N, T110P and L386I), and the T110P mutation results in N-glycosylation site silencing. WH2 was highly virulent in both unvaccinated and vaccinated animals in our pathogenesis experiments. Immunohistochemistry results revealed positive staining of different organs in unvaccinated and vaccinated animals. The serum in vitro neutralizing antibody titers for the vaccinated mink group and a dog were higher for the WH2 strain than those of the HNly150520B strain (isolated from a dog). These findings indicate that the current commercial vaccines provide incomplete protection against WH2 challenge infections. Thus, a new vaccine strain is urgently needed to protect against variant CDV strains.


Assuntos
Vírus da Cinomose Canina/isolamento & purificação , Cinomose/virologia , Vison/virologia , Vacinas Virais/efeitos adversos , Animais , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/farmacologia , Cinomose/genética , Vírus da Cinomose Canina/patogenicidade , Cães , Genótipo , Vison/genética , Filogenia , Vacinação/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/farmacologia
13.
Vaccine ; 39(27): 3633-3640, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33992437

RESUMO

BACKGROUND AND AIMS: ROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia. METHODS: We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose. RESULTS: The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period. CONCLUSIONS: Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Anticorpos Antivirais , Humanos , Imunogenicidade da Vacina , Índia , Lactente , Recém-Nascido , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Zâmbia
14.
Viruses ; 13(3)2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801868

RESUMO

Classical swine fever (CSF), caused by CSF virus (CSFV), is one of the most devastating viral epizootic diseases of swine in many countries. To control the disease, highly efficacious and safe live attenuated vaccines have been used for decades. However, the main drawback of these conventional vaccines is the lack of differentiability of infected from vaccinated animals (DIVA concept). Advances in biotechnology and our detailed knowledge of multiple basic science disciplines have facilitated the development of effective and safer DIVA vaccines to control CSF. To date, two types of DIVA vaccines have been developed commercially, including the subunit vaccines based on CSFV envelope glycoprotein E2 and chimeric pestivirus vaccines based on infectious cDNA clones of CSFV or bovine viral diarrhea virus (BVDV). Although inoculation of these vaccines successfully induces solid immunity against CSFV, none of them could ideally meet all demands regarding to safety, efficacy, DIVA potential, and marketability. Due to the limitations of the available choices, researchers are still striving towards the development of more advanced DIVA vaccines against CSF. This review summarizes the present status of candidate CSFV vaccines that have been developed. The strategies and approaches revealed here may also be helpful for the development of new-generation vaccines against other diseases.


Assuntos
Vírus da Febre Suína Clássica/imunologia , Peste Suína Clássica/prevenção & controle , Doenças dos Suínos/prevenção & controle , Vacinas Atenuadas/imunologia , Vacinas de Subunidades/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Peste Suína Clássica/imunologia , Gado/virologia , Vacinação em Massa , Suínos , Doenças dos Suínos/virologia , Vacinas Atenuadas/efeitos adversos , Vacinas de Subunidades/efeitos adversos , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
15.
Hum Vaccin Immunother ; 17(7): 2311-2318, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-33545015

RESUMO

Background Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity.Methods This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6-12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA).Results The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups.Conclusions The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Adulto , Anticorpos Antivirais , China , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Lactente , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Vacinas Combinadas
16.
Transbound Emerg Dis ; 68(3): 1363-1376, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32810924

RESUMO

Brucellosis is an important occupational disease, mainly among veterinarians, because of their frequent contact with sick animals, contaminated secretions and live attenuated anti-Brucella vaccines. This study aimed to determine the prevalence of accidental exposure to S19 and RB51 vaccine strains and occupational brucellosis among veterinarians registered to administer vaccinations in Minas Gerais, Brazil, as well as to identify the risk factors associated with accidental exposure to anti-Brucella abortus vaccines. Data were collected through an online questionnaire. Three hundred and twenty-nine veterinarians were included in the analyses using stratified random sampling. A multivariate logistic regression analysis was used to evaluate the predictors of accidental exposure to S19 and RB51 strains. Nearly one third of the veterinarians registered to administer bovine brucellosis vaccination in Minas Gerais, 32.83% (108/329) (95% confidence interval [CI]: 27.78-38.19%), reported having been accidentally exposed to S19 or RB51 vaccine strains. The exposure factors associated with this outcome included a score of personnel protective equipment (PPE) use during work (odds ratio [OR], 0.94; 95% CI: 0.89-0.98) and a score of knowledge about brucellosis symptoms, classified as poor (base category), intermediate (OR, 0.26; 95% CI: 0.07-0.87) or good (OR, 0.22; 95% CI: 0.07-0.62). In addition, 4.56% (15/329) (95% CI: 2.57-7.41%) of veterinarians reported that they had brucellosis, of which 46.67% (7/15) considered that the disease was due to accidental exposure to anti-B. abortus live attenuated vaccine. The prevalence of accidental exposure to B. abortus vaccine strains among veterinarians from Minas Gerais enrolled in the control of bovine brucellosis was high. The reduced knowledge about human brucellosis symptoms and lack of appropriate PPE use were risk factors from unintentional contact with S19 and RB51 vaccine strains.


Assuntos
Vacina contra Brucelose/efeitos adversos , Brucella abortus/fisiologia , Brucelose/epidemiologia , Doenças Profissionais/epidemiologia , Médicos Veterinários/estatística & dados numéricos , Adulto , Brasil , Brucelose/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/microbiologia , Vacinas Atenuadas/efeitos adversos
17.
Nature ; 590(7845): 320-325, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33260195

RESUMO

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vetores Genéticos/genética , SARS-CoV-2/imunologia , Vacinas Atenuadas/imunologia , Vacina contra Febre Amarela/genética , Animais , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/genética , Cricetinae , Modelos Animais de Doenças , Feminino , Glicosilação , Macaca fascicularis/genética , Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Masculino , Mesocricetus/genética , Mesocricetus/imunologia , Mesocricetus/virologia , Camundongos , Segurança , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/genética
18.
Vaccine ; 39(4): 746-750, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33267969

RESUMO

INTRODUCTION: In 2006 and 2008, two live, oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), were introduced into the routine immunization program in the United States. A previous rotavirus vaccine, RotaShield, was associated with an increased risk of intussusception, with data suggesting an age-dependent variation in risk. Advisory Committee on Immunization Practices (ACIP) currently recommends that RV5 or RV1 immunization be initiated by age 14 weeks and 6 days and completed by 8 months 0 days. METHODS: We searched for U.S. VAERS reports of RV5, RV1, or unknown rotavirus vaccine brand among individuals aged ≥8 months. We analyzed reports by 2 age groups (individuals aged ≥8 months-≤5 years and ≥6 years), vaccine brand name, adverse event (AE) reported, classification of seriousness (death, non-death serious, and non-serious) and mode of exposure (direct vs. indirect exposure). For serious reports we reviewed available medical records and assigned a primary diagnosis. RESULTS: VAERS received a total of 344 U.S. reports following rotavirus vaccination among individuals ≥8 months of age, 32 (9.3%) were serious. In the younger age-group, 307 (99%) of 309 reports followed direct vaccination of the child. In contrast, in individuals aged ≥6 years, 21 (60%) of 35 reports were via potential indirect exposure to a vaccinated child. The frequently reported AEs in the younger age-group were inappropriate schedule of drug administration 104 (34%) and drug administered to patient of inappropriate age 45 (15%); in the older group these were accidental exposure 9 (26%) and eye irritation 7 (20%). No difference in the safety profile was observed between RV1 and RV5. CONCLUSIONS: We did not identify any unexpected AEs for RV vaccines among individuals aged ≥8 months. Health care providers should adhere to the ACIP recommended schedule and older individuals should apply necessary precautions to prevent potential secondary exposure from vaccinated children.


Assuntos
Intussuscepção , Infecções por Rotavirus , Vacinas contra Rotavirus , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Criança , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Intussuscepção/induzido quimicamente , Intussuscepção/epidemiologia , Pessoa de Meia-Idade , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Estados Unidos/epidemiologia , Vacinas Atenuadas/efeitos adversos
19.
Am J Trop Med Hyg ; 104(1): 283-293, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33205741

RESUMO

Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. Plasmodium falciparum sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 106 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 105 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7-13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, P = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.


Assuntos
Imunogenicidade da Vacina , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Antiprotozoários , Antimaláricos/uso terapêutico , Criança , Pré-Escolar , Cloroquina/uso terapêutico , Método Duplo-Cego , Guiné Equatorial/epidemiologia , Feminino , Humanos , Imunização , Lactente , Vacinas Antimaláricas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Parasitemia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Adulto Jovem
20.
J Med Primatol ; 50(1): 36-45, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33219623

RESUMO

BACKGROUND: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP). METHODS: Susceptible howler monkeys were immunized with three different concentrations of the human Brazilian commercial YF17DD vaccine. Post-vaccination viremia/RNAemia, immunogenicity, and safety were characterized. RESULTS: The vaccine did not produce YF clinical manifestations in any of the NHPs. After immunization, all animals seroconverted demonstrating the ability of the YF vaccine to induce humoral response in Alouatta species. CONCLUSIONS: The present work has demonstrated the safe and immunogenic profile of the existing YF 17DD vaccine in howler monkeys. This knowledge may support further studies with other susceptible monkey species and provide a possible solution for controlling epizootics and preventing the devastation of endangered species.


Assuntos
Alouatta/imunologia , Imunogenicidade da Vacina , Vacina contra Febre Amarela/efeitos adversos , Animais , Feminino , Masculino , Especificidade da Espécie , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacina contra Febre Amarela/imunologia
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