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1.
BMC Health Serv Res ; 22(1): 34, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986870

RESUMO

BACKGROUND: The decision to implement new vaccines should be supported by public health and economic evaluations. Therefore, this study was primarily designed to evaluate the economic impact of switching from partially combined vaccine (Pentaxim® plus hepatitis B) to fully combined vaccine (Hexaxim®) in the Malaysian National Immunization Program (NIP) and to investigate healthcare professionals (HCPs)' and parents'/caregivers' perceptions. METHODS: In this economic evaluation study, 22 primary healthcare centers were randomly selected in Malaysia between December 2019 and July 2020. The baseline immunization schedule includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses), whereas the alternative scheme includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses) and hepatitis B (one dose) administered at birth. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct non-medical (cost for transportation) and indirect costs (loss of productivity) were derived from parents'/caregivers' questionnaire. Also, HCPs' and parent's/caregivers' perceptions were investigated using structured questionnaires. RESULTS: The cost per dose of Pentaxim® plus hepatitis B vs. Hexaxim® for the baseline scheme was Malaysian ringgit (RM) 31.90 (7.7 United States dollar [USD]) vs. 17.10 (4.1 USD) for direct medical cost, RM 54.40 (13.1 USD) vs. RM 27.20 (6.6 USD) for direct non-medical cost, RM 221.33 (53.3 USD) vs. RM 110.66 (26.7 USD) for indirect cost, and RM 307.63 (74.2 USD) vs. RM 155.00 (37.4 USD) for societal (total) cost. A similar trend was observed for the alternative scheme. Compared with Pentaxim® plus hepatitis B, total cost savings per dose of Hexaxim® were RM 137.20 (33.1 USD) and RM 104.70 (25.2 USD) in the baseline and alternative scheme, respectively. Eighty-four percent of physicians and 95% of nurses supported the use of Hexaxim® in the NIP. The majority of parents/caregivers had a positive perception regarding Hexaxim® vaccine in various aspects. CONCLUSIONS: Incorporation of Hexaxim® within Malaysian NIP is highly recommended because the use of Hexaxim® has demonstrated substantial direct and indirect cost savings for healthcare providers and parents/caregivers with a high percentage of positive perceptions, compared with Pentaxim® plus hepatitis B. TRIAL REGISTRATION: Not applicable.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche , Hepatite B , Análise Custo-Benefício , Vacinas Anti-Haemophilus , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vacinas contra Hepatite B , Humanos , Programas de Imunização , Recém-Nascido , Vacina Antipólio de Vírus Inativado , Vacinas Combinadas
2.
Vet Microbiol ; 264: 109305, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34923248

RESUMO

The present study was undertaken to quantify the Marek's Disease Virus (MDV) serotypes in vaccinated commercial layer flocks at 7, 14, 21, 28, 35 and 60-90 days post vaccination (dpv) and to correlate the pathogenic Gallid herpesvirus 2 (GaHV-2, MDV1) load with vaccine viral load of Gallid herpesvirus 3 (GaHV-3, MDV2) and Meleagridis herpesvirus 1 (MeHV-1, MDV3). A total of 25 commercial layer flocks were selected in and around Namakkal district of Tamil nadu, India and the feather pulp (FP) and blood samples were collected. Out of 25 flocks, 14 were revaccinated with bivalent vaccine, six were revaccinated with monovalent vaccine apart from the initial bivalent vaccination done at hatchery and five flocks were not revaccinated. SYBR green based real time PCR was used for absolute quantification of MDV serotypes. The pathogenic MDV1 load had shown an increasing trend until 21 dpv followed by a dip and again had shown a constant uptick between 60 and 90 dpv in the flocks that went on to develop MD outbreak. The flocks which had not encountered any Marek's Disease outbreak had shown increasing trend of MDV2 and 3 load until 21 dpv followed by a slight decrease but maintained a higher load when compared to MDV 1 which had marked a sharp decline between 60 and 90 dpv. Outbreak of MD was observed in seven (28%) out of 25 flocks between 18 and 27 weeks of age. It includes, two out of fourteen farms (14%) revaccinated with bivalent vaccine, two out of six farms (33%) revaccinated with MDV3 vaccine and three out of five farms (60%) without revaccination. The overall mean of vaccine viral load at various stages of dpv was constantly low where as pathogenic MDV 1 load was constantly high between 60 and 90 dpv in the flocks that went on to develop Marek's Disease during later part of life.


Assuntos
Herpesvirus Galináceo 2 , Doença de Marek , Animais , Galinhas/imunologia , Herpesvirus Galináceo 2/fisiologia , Índia , Doença de Marek/epidemiologia , Doença de Marek/prevenção & controle , Vacinação/veterinária , Vacinas Combinadas
3.
Methods Mol Biol ; 2414: 151-169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34784037

RESUMO

Vaccines are regarded as the most cost-effective countermeasure against infectious diseases. One challenge often affecting vaccine development is antigenic diversity or pathogen heterogeneity. Different strains produce immunologically heterogeneous virulence factors, therefore an effective vaccine needs to induce broad-spectrum host immunity to provide cross-protection. Recent advances in genomics and proteomics, particularly computational biology and structural biology, establishes structural vaccinology and highlights the feasibility of developing effective and precision vaccines. Here, we introduce the epitope- and structure-based vaccinology platform multiepitope-fusion-antigen (MEFA), and provide instructions to generate polyvalent MEFA immunogens for vaccine development. Conceptually, MEFA combines epitope vaccinology and structural vaccinology to enable a protein immunogen to present heterogeneous antigenic domains (epitopes) and to induce broadly protective immunity against different virulence factors, strains or diseases. Methodologically, the MEFA platform first identifies a safe, structurally stable and strongly immunogenic backbone protein and immunodominant (ideally neutralizing or protective) epitopes from heterogeneous strains or virulence factors of interest. Then, assisted with protein modeling and molecule dynamic simulation, MEFA integrates heterogeneous epitopes into a backbone protein via epitope substitution for a polyvalent MEFA protein and mimics epitope native antigenicity. Finally, the MEFA protein is examined for broad immunogenicity in animal immunization, and assessed for potential application for multivalent vaccine development in preclinical studies.


Assuntos
Vacinas Combinadas , Animais , Biologia Computacional , Diarreia , Escherichia coli Enterotoxigênica/imunologia , Epitopos/genética , Infecções por Escherichia coli , Vacinologia , Fatores de Virulência/genética
4.
Ig Sanita Pubbl ; 79(5): 625-638, 2021.
Artigo em Italiano | MEDLINE | ID: mdl-34919537

RESUMO

Invasive meningococcal disease (IMD) is caused by 6 serogroups of the bacterium Neisseria meningitidis (A, B, C, W, X and Y). It is among the most serious vaccine preventable infectious diseases, characterized by a high case-fatality rate and risk of permanent sequelae. Worldwide, the incidence of IMD is generally low with differences among regions and age groups. The risk increases in overcrowded conditions or in case of travel to endemic areas. The first vaccines produced using polysaccharide capsular antigens have demonstrated a good protective efficacy, but of short lenght. The conjugation of antigens with proteins allowed to obtain a longlasting antibody response towards 4 serogroups: A, C, W, Y. Currently four ACWY quadrivalent conjugate vaccines are available, three of them approved in Europe, which have shown high immunogenicity and safety. In 2020 the MenACYW-TT vaccine conjugated to tetanus toxoid was approved in the USA and it is presently authorized in Europe for the immunization of individuals from 12 months of age. Clinical studies have demonstrated immunogenicity and safety on population samples belonging to different age groups and non-inferiority in comparing it with other vaccines already in use. The possibility of having an increasing number of safe, immunogenic and effective vaccines against IMD allows us to imagine a future without invasive meningococcal disease. It is therefore important to extend vaccination to an increasing number of subjects of different age groups and risk conditions.


Assuntos
Infecções Meningocócicas , Europa (Continente) , Humanos , Infecções Meningocócicas/prevenção & controle , Vacinas Combinadas , Vacinas Conjugadas
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(5): 948-954, 2021 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814494

RESUMO

Combined vaccines contain two or more antigens. Research suggested that combined vaccines could prevent multi diseases and reduce the frequency of vaccination. This article focus on combined vaccines for children used both at home and abroad, such as diphtheria-pertussis-tetanus vaccine (DTaP), measles-rubella-mumps vaccine (MMR), etc. and summarizes their immunogenicity, safety and social values, including benefits to families, vaccination workers and health services, to provide evidence for promoting the research, development and use of combined vaccines in China. We found that combined vaccines can not only ensure the immunogenicity and safety, but also give convenient and lower cost vaccination to families, and using combined vaccines can improve the work efficiency of vaccination workers, reduce the impact of the epidemic on immunization services and improve vaccination coverage and timeliness. At present, the promotion of combined vaccines in China is restricted by many technical bottlenecks, high prices, and low awareness among people. It is recommended that research on the safety, effectiveness and health economics of combined vaccines should be strengthened, and the value of combined vaccines should be scientifically evaluated; the public's awareness and trust in combined vaccines should be enhanced, as well as the development and application of multi-linked multivalent vaccines should be promoted. The government should improve regulations to assist the development and application of combined vaccines.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Valores Sociais , Criança , Humanos , Lactente , Vacina contra Sarampo-Caxumba-Rubéola , Vacina Antipólio de Vírus Inativado , Vacinação , Vacinas Combinadas
6.
ACS Infect Dis ; 7(11): 3111-3123, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34633812

RESUMO

Group B Streptococcus (GBS) is a leading cause of neonatal infections and invasive diseases in nonpregnant adults worldwide. Developing a protective conjugate vaccine targeting the capsule of GBS has been pursued for more than 30 years; however, it has yet to yield a licensed product. In this study, we present a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine and its subsequent analytical and immunological characterizations. Using a glycoengineering strategy, we generated strains of Escherichia coli that recombinantly express the type Ia, type Ib, and type III GBS capsular polysaccharides. We then combined the type Ia-, Ib-, and III-capsule-expressing E. coli strains with an engineered Pseudomonas aeruginosa exotoxin A (EPA) carrier protein and the PglS oligosaccharyltransferase. Coexpression of a GBS capsule, the engineered EPA protein, and PglS enabled the covalent attachment of the target GBS capsule to an engineered serine residue on EPA, all within the periplasm of E. coli. GBS bioconjugates were purified, analytically characterized, and evaluated for immunogenicity and functional antibody responses. This proof-of-concept study signifies the first step in the development of a next-generation multivalent GBS bioconjugate vaccine, which was validated by the production of conjugates that are able to elicit functional antibodies directed against the GBS capsule.


Assuntos
Escherichia coli , Infecções Estreptocócicas , Adulto , Anticorpos Antibacterianos , Escherichia coli/genética , Humanos , Recém-Nascido , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae/genética , Vacinas Combinadas
8.
Int J Pharm ; 609: 121143, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34600051

RESUMO

Establishing product stability is critical for pharmaceuticals. We used a modeling approach to predict the thermal stability of a fully-liquid quadrivalent meningococcal (serogroups A, C, W, Y) conjugate vaccine (MenACYW-TT; MenQuadfi®) at potential transportation and storage temperatures. Vaccine degradation was determined by measuring the rate of hydrolysis through an increase of free polysaccharide (de-conjugated or unconjugated polysaccharide) content during six months storage at 25 °C, 45 °C and 56 °C. A procedure combining advanced kinetics and statistics was used to screen and compare kinetic models describing observed free polysaccharide increase as a function of time and temperature for each serogroup. Statistical analyses were used to quantify prediction accuracy. A two-step kinetic model described the increase in free polysaccharide content for serogroup A; whereas, one-step kinetic models were found suitable to describe the other serogroups. The models were used to predict free polysaccharide increases for each serogroup during long-term storage under recommended conditions (2-8 °C), and during temperature excursions to 25 °C or 40 °C. In both cases, serogroup-specific simulations accurately predict the respective observed experimental data. Experimental data collected to 48 months at 5 °C were within 99% predictive bands. The models described here can be used with confidence to establish shelf-life for this fully-liquid quadrivalent meningococcal conjugate vaccine; as well as, monitor in real-time free polysaccharide increase for vaccines experiencing temperature excursions during shipment/storage.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Anticorpos Antibacterianos , Humanos , Toxoide Tetânico , Vacinas Combinadas , Vacinas Conjugadas
9.
Vaccine ; 39(45): 6644-6652, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34642087

RESUMO

Conjugation of carbohydrate antigens with a carrier protein is a clinically proven strategy to overcome the poor immunogenicity of bacterial polysaccharide. In addition to its primary role, which is to help generate a T cell-mediate long-lasting immune response directed against the carbohydrate antigen, the carrier protein in a glycoconjugate vaccine can also play an important role as a protective antigen. Among carrier proteins currently used in licensed conjugate vaccines, non-typeable Haemophilus influenzae protein D has been used as an antigenically active carrier protein. Our previous studies also indicate that some carrier proteins provide B cell epitopes, along with T cell helper epitopes. Herein we investigated the dual role of truncated rotavirus spike protein ΔVP8* as a carrier and a protective antigen. Capsular polysaccharide lipoarabinomannan (LAM), purified from Mycobacterium tuberculosis (M.tb), was chemically conjugated with ΔVP8*. Mouse immunization experiments showed that the resultant conjugates elicited strong and specific immune responses against the polysaccharide antigen, and the responses were comparable to those induced by Diphtheria toxoid (DT)-based conjugates. The conjugate vaccine induced enhanced antibody titers and functional antibodies against ΔVP8* when compared to immunization with the unconjugated ΔVP8*. Thus, these results indicate that ΔVP8* can be a relevant carrier protein for glycoconjugate vaccine and the glycoconjugates consisting of ΔVP8* with LAM are effective bivalent vaccine candidates against rotavirus and tuberculosis.


Assuntos
Vacinas Anti-Haemophilus , Mycobacterium tuberculosis , Rotavirus , Tuberculose , Animais , Anticorpos Antibacterianos , Diarreia , Camundongos , Polissacarídeos Bacterianos , Tuberculose/prevenção & controle , Vacinas Combinadas , Vacinas Conjugadas
10.
Front Immunol ; 12: 718895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512642

RESUMO

Background: Efficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS). Objective: To assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF). Methods: In this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs). The primary endpoints were responder rate of strain-specific antibody production (seroconversion or significant (4-fold) increase in influenza-antibody titers for ≥2/4 strains) at 30 days post-vaccination and changes in sNfL levels. Results: All patients treated with DMF fulfilled the responder criteria for immunization compared with 53% of the controls. However, higher proportions of HCs already had influenza-antibody titers ≥1:40 at baseline (53% vs. 41%, p = 0.174). sNfL levels were comparable among both groups at baseline and did not increase 34 days after vaccination. In addition, no clinical or radiological disease reactivation was found. Conclusion: DMF-treated patients mount an adequate humoral immune response to influenza vaccines. Within the limits of the small cohort investigated, our data suggest that influenza immunization is not associated with clinical or subclinical disease reactivation.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Esclerose Múltipla Recidivante-Remitente , Vacinas Combinadas/imunologia , Adulto , Anticorpos Antivirais/sangue , Fumarato de Dimetilo/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Soroconversão/fisiologia
11.
Front Immunol ; 12: 692937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497604

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising epitopes. Among them, ORF9b B-cell and T-cell epitopes are the most promising followed by M.ext and ORF3c epitopes. ORF9b40-48 (CD8+ T-cell epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell epitopes. Structure-based B-cell epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell epitopes (ORF9b65-69). ORF3c CD4+ T-cell epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell epitope (ORF3c14-22) have also been identified as the candidate epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext epitopes are finally shortlisted as potent epitopes. Mutation analysis has further revealed that the shortlisted potent uORF epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell epitopes identified here along with canonical ORF epitopes may aid in the design of a promising epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.


Assuntos
Antígenos Virais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , SARS-CoV-2/imunologia , Sequência de Aminoácidos/genética , Antígenos Virais/genética , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/uso terapêutico , Biologia Computacional , Proteínas do Nucleocapsídeo de Coronavírus/genética , Desenho de Fármacos , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Fases de Leitura Aberta/genética , Fases de Leitura Aberta/imunologia , SARS-CoV-2/genética , Análise de Sequência de Proteína , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia
13.
Vaccine ; 39(41): 6025-6036, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34531081

RESUMO

BACKGROUND: Three hexavalent vaccines against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib) are licensed in Europe: Infanrix hexa (DT3aP-HBV-IPV/Hib), Hexyon (DT2aP-HBV-IPV-Hib) and Vaxelis (DT5aP-HBV-IPV-Hib). METHODS: A systematic literature search was performed in various electronic databases to identify published peer-reviewed head-to-head studies comparing any licensed hexavalent vaccine to another. RESULTS: Predefined inclusion criteria were met by 12 articles. Individual studies concluded that the 3 hexavalent vaccines have acceptable safety profiles although some significant differences were observed in their reactogenicity profiles. The immunogenicity of DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib was non-inferior versus DT3aP-HBV-IPV/Hib. Some differences in immune responses to common antigens were observed, but their clinical relevance was not established. Anti-filamentous hemagglutinin (FHA) from pertussis and anti-polyribosylribitol phosphate (PRP) from Hib antibody concentrations tended to be higher, and anti-HBV and anti-pertussis toxin (PT) from pertussis antibody concentrations lower in DT2aP-HBV-IPV-Hib versus DT3aP-HBV-IPV/Hib vaccinees. Anti-PT and post-primary anti-PRP antibody concentrations tended to be higher, and anti-HBV, anti-FHA, anti-pertactin from pertussis and post-booster anti-PRP antibody concentrations lower in DT5aP-HBV-IPV-Hib versus DT3aP-HBV-IPV/Hib recipients. Slightly lower immune responses towards most vaccine antigens were observed with 2 + 1 versus 3 + 1 schedules post-primary vaccination, suggesting that 2 + 1 schedules should only be considered in countries with very high vaccination coverage. CONCLUSION: Although the licensed hexavalent vaccines are generally considered similar, analyses of immunogenicity data from head-to-head trials highlighted differences that could be related to differences in composition and formulation. In addition, the demonstrated non-inferiority of the immunogenicity of the more recent vaccines versus DT3aP-HBV-IPV/Hib does not allow a full bridging to similar efficacy, effectiveness and safety. The availability of DT3aP-HBV-IPV/Hib over > 20 years allowed to collect a wealth of data on its long-term immunogenicity, safety and effectiveness in clinical and post-marketing studies, and makes it a key pillar of pediatric immunization.


Assuntos
Difteria , Haemophilus influenzae tipo b , Hepatite B , Tétano , Criança , Difteria/prevenção & controle , Humanos , Vacinas Combinadas
14.
Schweiz Arch Tierheilkd ; 163(9): 545-552, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34465558

RESUMO

INTRODUCTION: The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horses (7%). Many of the reports in dogs involved the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with canine leptospira components, in cats against cat flu and feline panleukopenia in combination with feline leukaemia virus infection. Causality assessments were done according to the international ABON system. In 27% of the reported cases, the causality assessments between the vaccination and the reaction described were evaluated as being probable (ABON A), in 44% as possible (ABON B).


Assuntos
Vacinas , Drogas Veterinárias , Vacinas Virais , Animais , Bovinos , Cães , Cavalos , Suíça , Vacinação/efeitos adversos , Vacinação/veterinária , Vacinas/efeitos adversos , Vacinas Combinadas , Drogas Veterinárias/efeitos adversos , Vacinas Virais/efeitos adversos
15.
Value Health Reg Issues ; 26: 150-159, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34474265

RESUMO

OBJECTIVES: To evaluate cost implications of a hexavalent vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]-inactivated polio vaccine [IPV]-hepatitis B [HB]-Haemophilus influenzae type B [Hib] polysaccharide conjugated to T protein [PRP∼T]) as an alternative to DT-whole-cell pertussis (wP)-HB//Hib, DTwP, IPV, and oral polio vaccines in the Expanded Program on Immunization schedule in Colombia. METHODS: Primary vaccination (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV [2, 4, 6 months]) and booster (DTaP-IPV-HB-PRP∼T or DTwP + oral polio vaccine [18 months]) (scenario 1) and primary vaccination only (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV) (scenario 2) were evaluated. An estimated cost-minimization analysis was based on a micro costing technique for vaccination-associated activities. Adverse event (AE)-associated costs, out-of-pocket costs, and productivity losses for caregivers were included. A budget impact (12-month temporal horizon) was estimated according to the distribution of full-term and premature infants. A 5% annual discount rate was used. A 2-way univariate (tornado) analysis evaluated which variables had the greatest impact on the overall cost. RESULTS: DTaP-IPV-HB-PRP∼T resulted in a cost increase of 29.38% (scenario 1) and 22.19% (scenario 2) for full-term infants and a decrease of 0.99% (scenario 1) and 18.88% (scenario 2) for premature infants, probably because of the higher incidence of wP-related AEs and associated costs in premature infants. With a 100% replacement rate, the budget impact for full-term infants and full-term plus premature infants was 23.73% and 21.80% (scenario 1), respectively, and 13.02% and 11.14% (scenario 2), respectively, of the national immunization program budget. The variables with most impact were the hexavalent vaccine price and costs associated with the pentavalent safety profile. CONCLUSIONS: Incorporation of the hexavalent vaccine in the Expanded Program on Immunization schedule would lead to an increase in spending largely mitigated by reduced AE incidence and reduced logistic and social costs.


Assuntos
Programas de Imunização , Colômbia , Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Vacinas contra Hepatite B , Humanos , Imunização Secundária , Lactente , Vacina Antipólio de Vírus Inativado , Vacinas Combinadas
16.
Int J Pharm ; 609: 121126, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34560208

RESUMO

A bivalent Norovirus vaccine candidate has been developed that contains Norovirus strain GI.1 Norwalk-virus like particles (VLP) and strain GII.4 Consensus VLP adsorbed on aluminum (oxy)hydroxide. The Norwalk and Consensus antigens have different stability profiles, making it challenging to prepare a dry powder form of the Norovirus vaccine while maintaining the potency of both antigens. In the present study, we tested the feasibility of converting the vaccine from a liquid suspension to dry powders by thin-film freeze-drying (TFFD). With the proper amount of trehalose and/or sucrose as cryoprotectant (i.e. sucrose alone at 4.55% or 5.55%, w/v, or trehalose at 3-4% with 0.55% of sucrose), TFFD can be applied to successfully convert the Norovirus vaccine candidate into dry powders without causing antigen loss or particle aggregation, while maintaining the relative potency of both antigens within a specified acceptable range. In an accelerated stability study, the potency of the antigens was also maintained in the specified acceptable range after the dry powders prepared by TFFD in the presence of 5.55% (w/v) of sucrose were stored for eight weeks at 40 °C, 75% relative humidity. It is concluded that it is feasible to apply TFFD to convert the Norovirus vaccine from a liquid suspension to stable dry powders.


Assuntos
Norovirus , Vacinas , Liofilização , Pós , Vacinas Combinadas
17.
Vaccine ; 39(38): 5442-5446, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34373123

RESUMO

Italian born and long term resident in England, Sir Aldo Castellani (1874-1971), is usually credited with "several discoveries of great importance in tropical medicine", most notably for his role in determining the aetiology of sleeping sickness and yaws. This contribution tries to highlight his role in the history of vaccinology as a pioneer in the design and use of combined and polyvalent vaccines. In the light of existing data, while acting as Director of the Bacteriological Institute of Colombo (Ceylon) in the decade before the First World War, Castellani was the first to experiment with both different strains of "antigens belonging to the same group" like in his typhoid-paratyphoid vaccine (TAB), as well as the simultaneous use of more pathogens, or part of them, for protection against different diseases, like in his "tetravaccine" (TAB + cholera) and "pentavaccine" (TAB + cholera + Malta fever). At the beginning of the War, based on the results of thousands of vaccinations, he strongly maintained that those combined or mixed vaccines were harmless and effective. The Allied Armies became more and more interested in Castellani's methods. His TAB vaccine was extensively used among the soldiers and his contributions were largely acknowledged especially in the Anglo-Saxon world in the following years, when it was plainly stated that "to Castellani is due the credit of having first proposed, prepared, and used, combined vaccines". The path to widespread use of combination and polyvalent vaccines - which is usually dated back only to the late 1940s - was still long and winding. Castellani himself abandoned that field of research after the War and this is probably why that early history is nowadays often forgotten.


Assuntos
Cólera , Inventores , Vacinas , Cólera/prevenção & controle , Humanos , Itália , Masculino , Vacinas Combinadas
18.
Front Immunol ; 12: 688364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335590

RESUMO

Vaccination is a well-known trigger for mast cell degranulation in subjects affected by mastocytosis. Nevertheless, there is no exact standardized protocol to prevent a possible reaction after a vaccine injection, especially for patients who have already presented a previous vaccine-related adverse event, considering that these patients frequently tolerate future vaccine doses. For this reason, we aim to share our experience at Meyer Children's University Hospital in Florence to raise awareness on the potential risk for future vaccinations and to discuss the valuable therapeutic strategies intended to prevent them, taking into account what is proposed by experts in literature. We describe the case of an 18-month-old female affected by a polymorphic variant of maculopapular cutaneous mastocytosis that presented an extensive bullous cutaneous reaction 24 hours after the second dose (booster dose) of inactivated-tetravalent influenza vaccine, treated with a single dose of oral corticosteroid therapy with betamethasone (0.1 mg/kg) and an oral antihistamine therapy with oxatomide (1 mg/kg/daily) for a week, until resolution. To the best of our knowledge, in the literature, no documented case of reaction to influenza vaccine in maculopapular cutaneous mastocytosis is described. Subsequently, the patient started a background therapy with ketotifen daily (0.05 mg/kg twice daily), a non-competitive H1-antihistamine, and a mast cell stabilizer (dual activity). A non-standardized pharmacological premedication protocol with an H1-receptor antagonist (oxatomide, 0.5 mg/kg) administered 12 hours before the immunizations, and a single dose of betamethasone (0.05 mg/kg) together with another dose of oxatomide (0.5 mg/kg) administered 2 hours before the injections was followed to make it possible for the patient to continue with the scheduled vaccinations. Indeed, no reactions were subsequently reported. Thus, in our experience, a background therapy with ketotifen associated with a premedication protocol made by two doses of oxatomide and a single dose of betamethasone was helpful to make possible the execution of the other vaccines. We suggest how in these children, it could be considered the idea of taking precaution when vaccination is planned, regardless of the kind of vaccine and if a dose of the same vaccine was previously received. However, international consensus needs to be reached to manage vaccinations in children with mastocytosis and previous adverse reactions to vaccines.


Assuntos
Degranulação Celular , Liberação de Histamina , Imunização Secundária/efeitos adversos , Vacinas contra Influenza/efeitos adversos , Mastócitos/imunologia , Dermatopatias Vesiculobolhosas/induzido quimicamente , Urticaria Pigmentosa/imunologia , Vacinas Combinadas/efeitos adversos , Adolescente , Corticosteroides/administração & dosagem , Degranulação Celular/efeitos dos fármacos , Feminino , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Liberação de Histamina/efeitos dos fármacos , Humanos , Esquemas de Imunização , Vacinas contra Influenza/administração & dosagem , Mastócitos/efeitos dos fármacos , Pré-Medicação , Fatores de Risco , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Vesiculobolhosas/prevenção & controle , Resultado do Tratamento , Urticaria Pigmentosa/diagnóstico , Vacinas Combinadas/administração & dosagem
19.
Front Immunol ; 12: 692151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335601

RESUMO

Combining variant antigens into a multivalent vaccine is a traditional approach used to provide broad coverage against antigenically variable pathogens, such as polio, human papilloma and influenza viruses. However, strategies for increasing the breadth of antibody coverage beyond the vaccine are not well understood, but may provide more anticipatory protection. Influenza virus hemagglutinin (HA) is a prototypic variant antigen. Vaccines that induce HA-specific neutralizing antibodies lose efficacy as amino acid substitutions accumulate in neutralizing epitopes during influenza virus evolution. Here we studied the effect of a potent combination adjuvant (CpG/MPLA/squalene-in-water emulsion) on the breadth and maturation of the antibody response to a representative variant of HA subtypes H1, H5 and H7. Using HA protein microarrays and antigen-specific B cell labelling, we show when administered individually, each HA elicits a cross-reactive antibody profile for multiple variants within the same subtype and other closely-related subtypes (homosubtypic and heterosubtypic cross-reactivity, respectively). Despite a capacity for each subtype to induce heterosubtypic cross-reactivity, broader coverage was elicited by simply combining the subtypes into a multivalent vaccine. Importantly, multiplexing did not compromise antibody avidity or affinity maturation to the individual HA constituents. The use of adjuvants to increase the breadth of antibody coverage beyond the vaccine antigens may help future-proof vaccines against newly-emerging variants.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antígenos Virais/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Hemaglutininas/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas Combinadas/administração & dosagem , Animais , Anticorpos Antivirais/sangue , Ilhas de CpG , Cães , Feminino , Lipídeo A/administração & dosagem , Lipídeo A/análogos & derivados , Células Madin Darby de Rim Canino , Camundongos Endogâmicos C57BL , Oligodesoxirribonucleotídeos/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Esqualeno/administração & dosagem , Vacinas Sintéticas/administração & dosagem
20.
Avian Dis ; 65(1): 18-25, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-34339117

RESUMO

Severity of the tracheal histologic inflammatory response induced in broilers by ocular inoculation of two infectious bronchitis (IBV) and three Newcastle disease virus (NDV) commercial vaccines were evaluated. The vaccine was delivered by eye drop with a coarse spray to day-old chicks. The vaccines were given individually or in various combinations and were evaluated relative to nonvaccinated controls. Evaluations were performed on postvaccination (PV) days 7 and 14. Histologic endpoints included semiquantitative severity scoring of inflammatory components and quantitative morphometric determinations of inflammatory cell concentration, mucosal thickness, and percentage of ciliated mucosal surface. Strong positive correlations were observed between routine severity scoring and morphometric inflammatory parameters, whereas a negative correlation was present between inflammation severity and the percentage of mucosal ciliation. Variable, sometimes extensive, and often statistically significant differences in inflammatory responses were observed between the various vaccines. One IBV Massachusetts strain vaccine (IBV-A) produced the greatest overall inflammatory response when given alone or in combination with the NDV vaccines. Enhancement of tracheitis was seen on PV day 14 by covaccination of IBV-A with the NDV vaccines, but not by covaccination of another IBV Massachusetts strain vaccine (IBV-B) with NDV. Reduction in cilia percentage was observed for all vaccine groups relative to controls on PV day 7. However, although reactive cilia regeneration occurred on PV day 14 for most vaccine groups, a cilia regenerative response was not apparent for individual or NDV combination vaccination for IBV-A. The study also demonstrates that substantial microscopic trachea pathology may be present in vaccinated birds not exhibiting apparent clinical respiratory signs.


Assuntos
Galinhas , Infecções por Coronavirus/veterinária , Vírus da Bronquite Infecciosa/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Vacinas Virais/efeitos adversos , Animais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Doença de Newcastle/virologia , Doenças das Aves Domésticas/virologia , Traqueia/patologia , Traqueia/virologia , Vacinação/efeitos adversos , Vacinas Combinadas/efeitos adversos
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