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1.
MMWR Morb Mortal Wkly Rep ; 69(5): 136-139, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32027629

RESUMO

On December 21, 2018 the Food and Drug Administration (FDA) licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP) adsorbed, inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugate (meningococcal protein conjugate) and hepatitis B (HepB) (recombinant) vaccine, DTaP-IPV-Hib-HepB (Vaxelis; MCM Vaccine Company),* for use as a 3-dose series in infants at ages 2, 4, and 6 months (1). On June 26, 2019, after reviewing data on safety and immunogenicity, the Advisory Committee on Immunization Practices (ACIP)† voted to include DTaP-IPV-Hib-HepB in the federal Vaccines for Children (VFC) program.§ This report summarizes the indications for DTaP-IPV-Hib-HepB and provides guidance for its use.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Vacina Antipólio de Vírus Inativado/administração & dosagem , Pré-Escolar , Humanos , Esquemas de Imunização , Lactente , Licenciamento , Estados Unidos , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/administração & dosagem
2.
BMC Vet Res ; 15(1): 342, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619295

RESUMO

BACKGROUND: The objective of this study was to assess the efficacy of a trivalent vaccine mixture and compare it to the respective monovalent vaccines against Mycoplasma hyopneumoniae, porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). RESULTS: Pigs that were triple challenged with M. hyopneumoniae, PCV2, and PRRSV following vaccination with the trivalent vaccine mixture exhibited a significantly better growth performance when compared to unvaccinated and challenged pigs. A statistical difference was not found when comparing pig populations which were vaccinated with the trivalent vaccine followed by a triple challenge and pigs vaccinated with monovalent M hyopneumoniae vaccine followed by mycoplasmal single challenge in the following areas: M. hyopneumoniae nasal shedding, the number of M. hyopneumoniae-specific interferon-γ secreting cells (IFN-γ-SC), and mycoplasmal lung lesion scores. Pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge resulted in a similar reduction of PCV2 viremia, an increase in the number of PCV2-specific IFN-γ-SC and reduction in interstitial lung lesion scores when compared to pigs vaccinated with a PCV-2 vaccine and challenged with PCV2 only. Lastly, there was a significant difference in the reduction of PRRSV viremia, an increase in PRRSV-specific IFN-γ-SC and a reduction of interstitial lung lesion scores between pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge and pigs vaccinated with a monovalent PRRSV vaccine followed by PRRSV challenge only. CONCLUSION: The trivalent vaccine mixture was efficacious against a triple challenge of M. hyopneumoniae, PCV2, and PRRSV. The trivalent vaccine mixture, however, did not result in equal protection when compared against each respective monovalent vaccine, with the largest vaccine occurring within PRRSV.


Assuntos
Circovirus/imunologia , Mycoplasma hyopneumoniae/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Doenças dos Suínos/prevenção & controle , Vacinação/veterinária , Animais , Vacinas Bacterianas/imunologia , Infecções por Circoviridae/imunologia , Infecções por Circoviridae/prevenção & controle , Feminino , Masculino , Pneumonia Suína Micoplasmática/imunologia , Pneumonia Suína Micoplasmática/prevenção & controle , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Sus scrofa , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/virologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia , Vacinas Virais/imunologia
3.
Mem Inst Oswaldo Cruz ; 114: e180517, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30843921

RESUMO

BACKGROUND: Field testing required to license the combined measles, mumps, and rubella (MMR) vaccine must take into account the current recommendation of the vaccine in Brazil: first dose at 12 months and second dose at 15 months of age in combination with a varicella vaccine. OBJECTIVES: This study aimed to evaluate the clinical consistency, immunogenicity, and reactogenicity of three batches of MMR vaccine prepared with active pharmaceutical ingredients (API) from Bio-Manguinhos, Fiocruz (MMR-Bio), and compare it to a vaccine (MMR produced by GlaxoSmithKline) with different API. METHODS: This was a phase III, randomised, double-blind, non-inferiority study of the MMR-Bio administered in infants immunised at health care units in Pará, Brazil, from February 2015 to January 2016. Antibody levels were titrated by immunoenzymatic assays. Adverse events were recorded in diaries. FINDINGS: Seropositivity levels after MMR-Bio were 97.6% for measles, 84.7% for mumps, and 98.0% for rubella. After the MMRV vaccine, seroconversion rates and GMT increased substantially for mumps. In contrast, approximately 35% of the children had no detectable antibodies to varicella. Systemic adverse events were more frequent than local events. CONCLUSION: The demonstration of batch consistency and non-inferiority of the Bio-MMR vaccine completed the technology transfer. This is a significant technological achievement with implications for immunisation programs.


Assuntos
Vacina contra Varicela/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Varicela/prevenção & controle , Vacina contra Varicela/efeitos adversos , Vacina contra Varicela/imunologia , Método Duplo-Cego , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Caxumba/prevenção & controle , Rubéola (Sarampo Alemão)/imunologia , Rubéola (Sarampo Alemão)/prevenção & controle , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/imunologia
4.
Hum Vaccin Immunother ; 15(4): 800-808, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785851

RESUMO

Rotavirus infections have been reported to account for 40-50% of all hospitalized acute gastroenteritis cases in young children (<5 years) in Japan. Since 2011, Rotarix containing the live attenuated human rotavirus RIX4414 strain (HRV) has been licensed in Japan for infants. Vaccination against rotavirus is optional in Japan whereas administration of diphtheria, pertussis, tetanus, and inactivated poliovirus (DPT-IPV) vaccine is part of the national routine immunization program. In this open-label, randomized, controlled, multicenter study, we evaluated the immunogenicity and safety of the DPT-IPV vaccine (Squarekids) administered concomitantly or staggered with the liquid HRV (Rotarix) vaccine in healthy Japanese infants. A total of 292 infants aged 6-12 weeks were randomly assigned to receive DPT-IPV vaccine and HRV vaccine co-administered (n = 147) or staggered (n = 145). Immune responses to DPT-IPV vaccine were evaluated by measuring the post-vaccination serum antibody titers/concentrations to each antigen at one month following the third dose of DPT-IPV vaccine. Seroprotection/seropositivity against each of the diphtheria, pertussis (pertussis toxin and filamentous hemagglutinin), tetanus, and poliovirus type 1, 2 and 3 antigens was 92.8% or higher in both groups. In terms of immunogenicity, DPT-IPV vaccine co-administered with HRV vaccine was shown to be non-inferior to DPT-IPV vaccine with a staggered administration. The safety profile was comparable in the two vaccine groups with no vaccine-related serious adverse events, no deaths and no cases of intussusception. These results support co-administration of HRV vaccine with DPT-IPV vaccine in Japan. ClinicalTrials.gov NCT02907216.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Imunogenicidade da Vacina , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinas contra Rotavirus/administração & dosagem , Estudos de Coortes , Difteria/prevenção & controle , Feminino , Humanos , Imunização Secundária , Lactente , Japão , Masculino , Poliomielite/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Tétano/prevenção & controle , Vacinas Atenuadas/administração & dosagem , Vacinas Combinadas/administração & dosagem , Coqueluche/prevenção & controle
5.
Hum Vaccin Immunother ; 15(4): 786-799, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785357

RESUMO

In many countries, a second dose of a combined measles, mumps, and rubella (MMR) vaccine is recommended at 4-6 years of age - similarly to the booster of diphtheria, tetanus, acellular pertussis, and inactivated polio vaccine (DTaP-IPV) and the second dose of varicella vaccine (VV). Vaccine co-administration is generally encouraged if no interferences exist among the vaccines. This phase IIIa, randomized, controlled trial (NCT01621802) evaluated the immunogenicity and safety of MMR-RIT (Priorix, GSK) when given as a second dose with or without co-administration of DTaP-IPV and VV, using MMR II (M-M-R II, Merck & Co Inc.) as comparator. Antibody geometric mean concentrations or titers (GMCs/GMTs) and response rates to the components of all the administered vaccines were assessed. Solicited, unsolicited, and serious adverse events were recorded. Four thousand eleven children aged 4-6 years were enrolled. MMR-RIT elicited immune responses that were not inferior to those of MMR II in terms of GMCs and seroresponse rates when administered alone or when co-administered with DTaP-IPV and VV. The immune responses to the co-administered vaccines in MMR-RIT recipients were non-inferior to those in MMR II recipients. MMR-RIT and MMR II demonstrated similar reactogenicity profiles; the most frequent solicited adverse events across vaccine groups and sub-cohorts were local pain and fever. In conclusion, the immunogenicity and safety profiles of MMR-RIT administered with or without DTaP-IPV and VV were similar to those of MMR II.


Assuntos
Vacina contra Varicela/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Imunização Secundária , Imunogenicidade da Vacina , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina Antipólio de Vírus Inativado/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/imunologia , Vacina contra Varicela/imunologia , Criança , Pré-Escolar , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Esquema de Medicação , Feminino , Humanos , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Combinadas/administração & dosagem
6.
Vaccine ; 37(5): 698-704, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30626530

RESUMO

A parenteral inactivated rotavirus vaccine (IRV) in development could address three problems with current live oral rotavirus vaccines (ORV): their lower efficacy in low and middle-income countries (LMICs), lingering concerns about their association with intussusception, and their requirement for a separate supply chain with large volume cold storage. Adding a new parenteral IRV to the current schedule of childhood immunizations would be more acceptable if it could be combined with another injectable vaccine such as inactivated polio vaccine (IPV). Current plans for polio eradication call for phasing out oral polio vaccine (OPV) and transitioning to IPV, initially in LMICs as a single dose booster after two doses of OPV and ultimately as a two dose schedule. Today in many LMICs, IPV is administered as a standalone vaccine, which involves a separate cold chain and is relatively costly. We therefore tested in two animal models formulations of IPV with IRV to determine whether co-administration might interfere with the immune response to each product and spare antigen dose for both vaccines. Our results demonstrate that IRV when adjuvanted with alum and administered alone or in combination with IPV did not impair the immune responses to either rotavirus or poliovirus serotypes 1, 2 and 3. Similarly, IPV when formulated and administered alone or together with IRV induced comparable levels of neutralizing antibody to poliovirus type 1, 2 and 3. Furthermore, comparable antibody titers were observed in animals vaccinated with low, middle or high dose of IPV or IRV in combination. This dose sparing and the lack of interference between IPV and IRV administered together represent another step to support the further development of this novel combination vaccine for children.


Assuntos
Injeções Intramusculares , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Feminino , Cobaias , Esquemas de Imunização , Imunogenicidade da Vacina , Uso Off-Label , Poliovirus/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Ratos , Rotavirus/imunologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
7.
Hum Vaccin Immunother ; 15(5): 1145-1153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30668217

RESUMO

Infanrix-IPV (GSK, Belgium) is a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combination vaccine (DTaP-IPV) licensed in many countries including Korea. In accordance with Korean regulations, we conducted a post-marketing surveillance (PMS) to evaluate the safety of DTaP-IPV administered to Korean children in routine immunization schedules. Children aged <7 years receiving at least one dose of DTaP-IPV either as part of a primary (3-dose) vaccination series or as a subsequent booster were enrolled. Adverse events (AEs), adverse drug reactions (ADRs) and serious AEs (SAEs) were recorded after each dose during the 30-day post-vaccination follow-up period. Among a total of 639 children, 289 subjects (45.2%) experienced AEs, mostly (79.2%) assessed as being unlikely to be related to the vaccination. ADRs were reported in 13.0% of subjects. Fever was the most commonly reported expected AE (11.9% of subjects) and also the most commonly reported expected ADR (8.5% of subjects). No obvious association between AE incidence and vaccine dose sequence was apparent. An unexpected AE was seen in 32.9% of children, and unexpected ADRs were far less common (1.9%). Thirty-four SAEs were recorded in 26 subjects (4.1%), in two of whom a causal association with the vaccine could not be excluded, although both resolved quickly. Data from this PMS indicate that DTaP-IPV has an acceptable safety profile when given to Korean children in accordance with local prescribing recommendations in routine childhood immunization. ClinicalTrials.gov identifier: NCT01568060.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vigilância de Produtos Comercializados , Criança , Pré-Escolar , Difteria/prevenção & controle , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Feminino , Humanos , Imunização Secundária , Lactente , Masculino , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/efeitos adversos , Estudos Prospectivos , República da Coreia , Tétano/prevenção & controle , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Coqueluche/prevenção & controle
8.
Hum Vaccin Immunother ; 15(2): 327-338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30252603

RESUMO

This phase III, open-label, randomized study (NCT01978093) evaluated the immunogenicity and safety of co-administered Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (Hib-MenCY-TT) with human rotavirus vaccine (HRV), hepatitis A vaccine (HAV) and 13-valent pneumococcal conjugate vaccine (PCV13). We randomized 600 infants (1:1) to receive 4 doses of Hib-MenCY-TT at 2, 4, 6 and 12-15 months of age or 3 doses of Hib vaccine conjugated to N. meningitidis outer membrane protein complex (Hib-OMP) at 2, 4 and 12-15 months of age. All infants received HRV at 2 and 4 months of age, PCV13 at 2, 4, 6 and 12-15 months of age, HAV at 12-15 and 18-21 months of age, and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months of age. We measured immune responses against HRV, HAV and Hib with enzyme-linked immunosorbent assays, and against MenC/MenY with serum bactericidal assays using human complement. The 4-dose vaccination series with Hib-MenCY-TT induced a robust immune response against Hib, which was non-inferior to that induced by a 3-dose vaccination series with Hib-OMP, and against MenC and MenY. Hib-MenCY-TT did not interfere with immune responses to concomitantly administered HRV, PCV13 and HAV. We did not identify any safety concern. In conclusion, we showed that 4-dose vaccination series with Hib-MenCY-TT during infancy did not interfere with immune responses of co-administered HRV, PCV13 and HAV, induced robust immune responses against Hib, MenC and MenY, and had a clinically acceptable safety profile.


Assuntos
Vacinas Anti-Haemophilus/administração & dosagem , Vacinas contra Hepatite A/administração & dosagem , Imunogenicidade da Vacina , Vacinas Pneumocócicas/administração & dosagem , Vacinas contra Rotavirus/administração & dosagem , Toxoide Tetânico/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Feminino , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Masculino , Sorogrupo , Toxoide Tetânico/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
9.
Vaccine ; 37(1): 176-186, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30054160

RESUMO

BACKGROUND: We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent). METHODS: In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 µg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed. RESULTS: 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded. CONCLUSION: Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Imunogenicidade da Vacina , Imunoglobulina D/imunologia , Lipoproteínas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Haemophilus influenzae , Vacinas contra Hepatite B/administração & dosagem , Humanos , Imunização Secundária , Imunoglobulina D/genética , Lactente , Lipoproteínas/genética , Masculino , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/efeitos adversos , Vacina Antipólio de Vírus Inativado/administração & dosagem , Sorogrupo , Streptococcus pneumoniae , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
10.
Hum Vaccin Immunother ; 15(1): 235-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30118633

RESUMO

We evaluated antibody persistence against hepatitis B virus (HBV) in adolescents previously vaccinated with a hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib), as part of the national newborn immunization program in Germany. We also assessed the anamnestic response to a challenge dose of a monovalent HBV vaccine. In this phase 4, open-label, non-randomized study (NCT02798952), 302 adolescents aged 14-15 years, primed in their first 2 years of life with 4 DTPa-HBV-IPV/Hib doses, received one challenge dose of monovalent HBV vaccine. Blood samples were taken before and one month post-vaccination and used to determine antibody levels against hepatitis B surface antigen (HBs). Reactogenicity and safety were also assessed post-challenge dose. Pre-challenge dose, 53.7% of 268 participants included in the according-to-protocol cohort for immunogenicity had anti-HBs antibody concentrations ≥10 mIU/mL (seroprotection cut-off) and 16.8% had anti-HBs antibody concentrations ≥100 mIU/mL. One month post-challenge dose, 93.3% of adolescents had anti-HBs antibody concentrations ≥10 mIU/mL and 87.3% had antibody concentrations ≥100 mIU/mL. An anamnestic response was mounted in 92.5% of adolescents. Injection site pain (in 33.6% of participants) and fatigue (30.2%) were the most frequently reported solicited local and general symptoms, respectively. Six of the 55 unsolicited adverse events reported were considered vaccination-related. Two vaccination-unrelated serious adverse events were reported during the study. Long-term antibody persistence against hepatitis B was observed in 14-15 years old adolescents previously primed in infancy with DTPa-HBV-IPV/Hib. A challenge dose of monovalent HBV vaccine induced strong anamnestic response, with no safety concerns.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/imunologia , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Memória Imunológica , Vacina Antipólio de Vírus Inativado/imunologia , Adolescente , Anticorpos Antibacterianos/sangue , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Humanos , Esquemas de Imunização , Lactente , Recém-Nascido , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem , Fatores de Tempo , Vacinação/estatística & dados numéricos , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
11.
Hum Vaccin Immunother ; 15(4): 809-821, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30444673

RESUMO

Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis and Haemophilus influenzae type b vaccine (DTaP-HBV-IPV/Hib) can further reduce the number of injections in pediatric immunization schedules of countries currently using pentavalent DTaP combination vaccines. This open-label, randomized, multicenter study (NCT02096263) conducted in the United States evaluated the immunogenicity and safety of DTaP-HBV-IPV/Hib vaccine compared with concomitant administration of DTaP-HBV-IPV and HibA or DTaP-IPV/Hib and HBV vaccines. We randomized (1:1:1) infants to receive 3-dose priming with DTaP-HBV-IPV/Hib boosted with DTaP+ HibB, DTaP-HBV-IPV+ HibA boosted with DTaP+ HibA, or DTaP-IPV/Hib+ HBV boosted with DTaP-IPV/Hib, at 2, 4, 6, and 15-18 months of age. We enrolled and vaccinated 585 participants, 486 received a booster, and 476 completed the study. Of these, 466 participants were included in the primary and 408 in the booster according-to-protocol cohorts for immunogenicity. We demonstrated non-inferiority of DTaP-HBV-IPV/Hib vaccine to DTaP-HBV-IPV+ HibA co-administered vaccines in terms of geometric mean concentrations for pertussis antibodies post-primary vaccination. Post-primary vaccination, seroprotection/seropositivity rates for all vaccine antigens were similarly high between DTaP-HBV-IPV/Hib (≥ 94.8%), DTaP-HBV-IPV+ HibA (≥ 98.1%) or DTaP-IPV/Hib+ HBV (≥ 97.8%) groups. We observed robust immune responses post-booster, indicating effective priming by the 3 regimens. Reactogenicity was similar in the 3 groups. Twenty-eight serious adverse events were reported during the study; 3 were considered related to vaccination and resolved by the end of the study. These results confirm that DTaP-HBV-IPV/Hib could be a valuable additional source of pediatric DTaP, IPV, HBV, and Hib-containing vaccine in countries that currently use multivalent vaccines.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Imunização Secundária , Imunogenicidade da Vacina , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Combinadas/administração & dosagem , Difteria/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Feminino , Vacinas Anti-Haemophilus/efeitos adversos , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/efeitos adversos , Humanos , Esquemas de Imunização , Lactente , Masculino , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/efeitos adversos , Tétano/prevenção & controle , Estados Unidos , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/imunologia , Coqueluche/prevenção & controle
12.
Hum Vaccin Immunother ; 15(2): 317-326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30431387

RESUMO

We assessed the immunogenicity and safety of a three-dose primary vaccination schedule with the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Korean infants. In this phase III open-label, multicenter study (NCT01309646), healthy infants aged 42-69 days (randomized 1:1) received three doses of either pentavalent DTPa-IPV/Hib (DTPa-IPV/Hib group) or DTPa-IPV and Hib vaccines administered separately (DTPa-IPV+Hib group) at 2, 4, 6 months of age. The primary objective was to demonstrate non-inferiority of DTPa-IPV/Hib compared to DTPa-IPV+Hib vaccines in terms of immune responses to all vaccine antigens, 1 month post-dose 3. Solicited symptoms (local and general) were recorded during 4 days, and unsolicited adverse events (AEs) during 31 days, after each vaccination. Serious AEs (SAEs) were recorded throughout the study duration. The immunogenicity of the pentavalent DTPa-IPV/Hib vaccine was non-inferior compared to concomitant administration of DTPa-IPV+Hib vaccines. One month post-dose 3, nearly all infants had antibody levels above the seroprotective thresholds for anti-diphtheria toxoid, anti-tetanus toxoid, anti-polyribosyl-ribitol phosphate, and anti-poliovirus type 1, 2 and 3, and had antibody levels above the seropositive thresholds for anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies. A vaccine response for PT, FHA and PRN was observed in at least 96.7% of study participants. Anti-PRP geometric mean concentrations appeared lower for the DTPa-IPV/Hib group (8.456 µg/mL) than for the DTPa-IPV+Hib group (18.700 µg/mL). In both groups, the most common solicited symptoms were injection site redness and irritability. Fifty-seven SAEs were reported throughout the study; none were considered to be vaccination related.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/imunologia , Esquemas de Imunização , Imunogenicidade da Vacina , Vacina Antipólio de Vírus Inativado/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Relação Dose-Resposta Imunológica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Humanos , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem , República da Coreia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
13.
Vaccine ; 37(2): 280-288, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30503081

RESUMO

OBJECTIVE: To determine whether differences in combination DTaP vaccine types at 2, 4 and 6 months of age were associated with mortality (all-cause or non-specific), within 30 days of vaccination. DESIGN: Observational nationwide cohort study. SETTING: Linked population data from the Australian Childhood Immunisation Register and National Death Index. PARTICIPANTS: Australian infants administered a combination trivalent, quadrivalent or hexavalent DTaP vaccine (DTaP types) between January 1999 and December 2010 at 2, 4 and 6 months as part of the primary vaccination series. The study population included 2.9, 2.6, & 2.3 million children in the 2, 4 and 6 month vaccine cohorts, respectively. MAIN OUTCOME MEASURES: Infants were evaluated for the primary outcome of all-cause mortality within 30 days. A secondary outcome was non-specific mortality (unknown cause of death) within 30 days of vaccination. Non-specific mortality was defined as underlying or other cause of death codes, R95 'Sudden infant death syndrome', R96 'Other sudden death, cause unknown', R98 'Unattended death', R99 'Other ill-defined and unspecified cause of mortality' or where no cause of death was recorded. RESULTS: The rate of 30 day all-cause mortality was low and declined from 127.4 to 59.3 deaths per 100,000 person-years between 2 and 6 month cohorts. When compared with trivalent DTaP vaccines, no elevated risk in all-cause or non-specific mortality was seen with any quadrivalent or hexavalent DTaP vaccines, for any cohort. CONCLUSION: Use of routine DTaP combination vaccines with differing disease antigens administered during the first six months of life is not associated with infant mortality.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Mortalidade Infantil , Vacinação/estatística & dados numéricos , Coqueluche/prevenção & controle , Austrália/epidemiologia , Estudos de Coortes , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Registro Médico Coordenado , Sistema de Registros , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Coqueluche/epidemiologia
14.
Vaccine ; 37(1): 76-79, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30478005

RESUMO

BACKGROUND: Febrile seizures are associated with the first dose of measles-containing vaccines and the risk increases with chronologic age during the second year of life. We used the Vaccine Safety Datalink (VSD) to determine if the relative increase in risk of seizures following receipt of measles-containing vaccine differs by gestational age at birth. METHODS: Children were eligible if they received their first dose of measles-containing vaccine at age 12 through 23 months from January 2003 through September 2015. Children were excluded if they had a history of seizure or conditions strongly related to seizure prior to 12 months of age. Seizures were identified by diagnostic codes in the inpatient or emergency department settings. Using risk-interval analysis, we estimated the incidence rate ratio (IRR) for seizures in the 7 through 10 days (risk period) vs 15 through 42 days (control period) following receipt of measles-containing vaccines in children born preterm (<37 weeks gestation age) and those born full-term (≥37 weeks). RESULTS: There were 532,375 children (45,343 preterm and 487,032 full-term) who received their first dose of measles-containing vaccine at age 12 through 23 months. The IRRs of febrile seizures 7 through 10 days compared with 15 through 42 days after receipt of measles-containing vaccine were 3.9 (95% CI: 2.5-6.0) in preterm children and 3.2 (2.7-3.7) in full-term children; the ratio of IRRs: was 1.2 (0.76-1.9), p = 0.41. IRRs were also similar across gestational age groups, by vaccine type received (measles-mumps-rubella [MMR] or measles-mumps-rubella-varicella [MMRV]) and age at vaccination (12-15 or 16-23 months). CONCLUSION: Vaccination with a measles-containing vaccine in the second year of life is associated with a similar relative risk of a first seizure in children born preterm as in those who were born full-term.


Assuntos
Vacina contra Varicela/efeitos adversos , Recém-Nascido Prematuro , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Convulsões Febris/etiologia , Nascimento a Termo , Vacinação/efeitos adversos , Vacina contra Varicela/administração & dosagem , Feminino , Idade Gestacional , Humanos , Lactente , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Medição de Risco , Convulsões Febris/complicações , Estados Unidos , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos
15.
Hum Vaccin Immunother ; 15(4): 778-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30481110

RESUMO

This randomized trial conducted in France compared intramuscular (IM) and subcutaneous (SC) administration of two doses of a measles, mumps, rubella, and varicella (MMRV) combination vaccine (ProQuad®) administered one month apart to 405 children 12-18 months of age (NCT00402831). The 2-dose regimen of MMRV administered IM was shown to be as immunogenic as the 2-dose regimen administered SC for all antigens 6 weeks post-vaccination for the subjects who were initially seronegative for measles, mumps, rubella, or varicella (lower bounds of the two-sided 95% CIs for the difference in response rates for all antigens greater than -10% [range -2.1 for varicella to -3.0 for mumps]). The antibody response rates for all vaccine antigens 6 weeks after the second dose of MMRV were > 99% in both the IM and SC groups. Fewer subjects in the IM group experienced injection-site AEs compared with the SC group (17.8% and 28.6% post-dose 1, and 20.4% and 29.5% post-dose 2, respectively). From Day 0 to Day 4 post-dose 2, fewer subjects reported erythema and swelling in the IM group than in the SC group (15.4% and 27.0%, and 6.0% and 12.5%, respectively). In both groups, most injection-site AEs started during the first four days after vaccination; their intensity was mainly mild or ≤2.5 cm. The rates of fever were comparable between the two groups after each dose of MMRV. In conclusion, two doses of the MMRV vaccine were highly immunogenic and well tolerated when administered either SC or IM. ClinicalTrials.gov Identifier: NCT00402831.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Esquemas de Imunização , Imunogenicidade da Vacina , Injeções Intramusculares , Injeções Subcutâneas , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Varicela/prevenção & controle , Feminino , Febre/induzido quimicamente , França , Humanos , Lactente , Masculino , Sarampo/prevenção & controle , Rubéola (Sarampo Alemão)/prevenção & controle , Vacinação , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
16.
Hum Vaccin Immunother ; 15(3): 658-668, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30513252

RESUMO

OBJECTIVE: Antibody persistence evaluation for all antigens of a fully liquid DTaP-IPV-HB-PRP~T vaccine at 3.5 and 4.5 y of age following different primary series and booster schedules in South Africa and Latin America. METHODS: Participants had completed one of two previous studies (Study 1-South Africa; Study 2-Latin America). In Study 1, participants who had not received HB vaccine at birth received a 6-10-14 week primary series of DTaP-IPV-HB-PRP~T or DTwP/PRP~T-Hib+HB+OPV and a third group who had received HB vaccine at birth received a 6-10-14 week primary series of DTaP-IPV-HB-PRP~T; all received a booster (15-18 months) of the primary series vaccine(s) except for HB in the DTwP/PRP~T-Hib group. In Study 2, participants received HB vaccine at birth, a 2-4-6 month primary series of DTaP-IPV-HB-PRP~T or DTaP-HB-IPV//PRP~T, and a DTaP-IPV-HB-PRP~T or DTaP-HB-IPV//PRP~T booster (12-24 months). Participants were followed up at 3.5 and 4.5 y of age for antibody persistence. RESULTS: Approximately 80% of eligible participants were assessed. In Study 1, a birth dose of HB increased anti-HBs persistence (≥10 mIU/mL) following DTaP-IPV-HB-PRP~T primary and booster vaccination from 76.3% to 96.1% at 3.5 y of age and from 73.3% to 96.1% at 4.5 y of age; in Study 2, anti-HBs persistence was high and similar in each group. For the other antigens, there were no differences between groups or studies at 3.5 or 4.5 y. CONCLUSION: Good persistence of antibodies to each antigen in the DTaP-IPV-HB-PRP~T vaccine up to pre-school age, irrespective of the vaccination schedule during the first 2 y of life.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/imunologia , Esquemas de Imunização , Vacina Antipólio de Vírus Inativado/imunologia , Antígenos de Bactérias/imunologia , Antígenos Virais de Tumores/imunologia , Criança , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Humanos , Imunização Secundária , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem , Estudos Prospectivos , Fatores de Tempo , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
17.
BMC Public Health ; 18(Suppl 4): 1306, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30541514

RESUMO

BACKGROUND: The year 2014 was a turning point for polio eradication in Nigeria. Confronted with the challenges of increased numbers of polio cases detected in rural, hard-to-reach (HTR), and security-compromised areas of northern Nigeria, the Nigeria polio program introduced the HTR project in four northern states to provide immunization and maternal and child health services in these communities. The project was set up to improve population immunity, increase oral polio vaccine (OPV) and other immunization uptake, and to support Nigeria's efforts to interrupt polio transmission by 2015. Furthermore, the project also aimed to create demand for these services which were often unavailable in the HTR areas. To this end, the program developed a community engagement (CE) strategy to create awareness about the services being provided by the project. The term HTR is operationally defined as geographically difficult terrain, with any of the following criteria: having inter-ward/inter-Local Government Area/interstate borders, scattered households, nomadic population, or waterlogged/riverine area, with no easy to access to healthcare facilities and insecurity. METHODS: We evaluated the outcome of CE activities in Kano, Bauchi, Borno, and Yobe states to examine the methods and processes that helped to increase OPV and third pentavalent (penta3) immunization coverage in areas of implementation. We also assessed the number of community engagers who mobilized caregivers to vaccination posts and the service satisfaction for the performance of the community engagers. RESULTS: Penta3 coverage was at 22% in the first quarter of project implementation and increased to 62% by the fourth quarter of project implementation. OPV coverage also increased from 54% in the first quarter to 76% in the last quarter of the 1-year project implementation. CONCLUSIONS: The systematic implementation of a CE strategy that focused on planning and working with community structures and community engagers in immunization activities assisted in increasing OPV and penta3 immunization coverage.


Assuntos
Participação da Comunidade , Programas de Imunização/organização & administração , Imunização/estatística & dados numéricos , Unidades Móveis de Saúde , Criança , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacinas Anti-Haemophilus/administração & dosagem , Humanos , Nigéria , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Avaliação de Programas e Projetos de Saúde , Vacinas Combinadas/administração & dosagem
18.
Vaccine ; 36(52): 8019-8027, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30471953

RESUMO

Invasive meningococcal disease caused by Neisseria meningitidis is a life-threatening disease. Several countries now include meningococcal serogroup C (MenC) conjugate and, more recently, a meningococcal serogroup ACWY conjugate (MenACWY) vaccination in their national immunization schedules. DTaP-IPV-HB-PRP-T is a hexavalent vaccine that provides protection against six diseases. The phase III, open-label, randomised, multicentre study enrolled healthy toddlers who received the DTaP-IPV-HB-PRP-T vaccine (at 2, 3 and 4 months) with or without a MenC vaccine (at 2 and 4 months) in the primary series study. At 12 months of age, 312 toddlers were randomised to receive DTaP-IPV-HB-PRP-T co-administered with MenACWY-TT vaccine (Group A; n = 104); DTaP-IPV-HB-PRP-T vaccine alone (Group B; n = 105); or MenACWY-TT vaccine alone (Group C; n = 103). At 12 months of age, there were no notable differences in terms of antibody persistence for any DTaP-IPV-HB-PRP-T vaccine antigen, whether MenC-TT conjugate vaccine was co-administered or not during the primary series. Following booster vaccination, immune responses to DTaP-IPV-HB-PRP-T and MenACWY-TT vaccines were not affected by co-administration. One month after vaccination, the immune responses elicited by both vaccines were high, whether administered concomitantly or separately. The administration of MenC vaccine during infancy did not preclude the use of a MenACWY-TT vaccine for booster vaccination. Even though the reactogenicity after co-administration was somewhat higher, the results of this study support the concomitant administration of the DTaP-IPV-HB-PRP-T vaccine with a MenACWY-TT conjugate vaccine when given from 12 months of age. The clinical trial registration numbers are: clinicaltrial.gov: NCT01839175; EudraCT: 2012-005547-24.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacina Antipólio de Vírus Inativado/administração & dosagem , Anticorpos Antibacterianos/sangue , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/imunologia , Humanos , Esquemas de Imunização , Imunização Secundária , Imunogenicidade da Vacina , Lactente , Masculino , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo C/imunologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
19.
Lancet Infect Dis ; 18(11): 1260-1268, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30266329

RESUMO

BACKGROUND: The immunogenicity of acellular pertussis vaccines and persistence of immunity after vaccination might be improved by using genetically inactivated pertussis toxin (PTgen) instead of chemically inactivated pertussis toxin (PTchem) because of the preservation of conformational epitopes. We assessed the safety and immunogenicity of two vaccines containing PTgen 1 year after vaccination. METHODS: We did a phase 2/3 non-inferiority, randomised, controlled trial involving 450 adolescents (age 12-17 years) enrolled between July 6, 2015, and Aug 20, 2015. Participants were randomised 1:1:1 to receive one dose of vaccine containing PTgen and filamentous haemagglutinin (FHA) either in a monovalent formulation (aP[PTgen/FHA]) or in a combined formulation with tetanus and reduced-dose diphtheria toxoids (TdaP[PTgen/FHA]) or to receive a commercial vaccine containing reduced-dose PTchem (Tdap) as a comparator. We report a secondary trial outcome, namely antibody persistence 1 year after vaccination, assessed per protocol in 150 randomly preselected participants (50 per group). Seroconversion was defined as antibody titres at least four times greater than at baseline. Safety was assessed in all trial participants. This study is registered in the Thai Clinical Trial Registry, number TCTR20150703002. FINDINGS: Between June 5, 2016, and Aug 9, 2016, 442 (98%) of 450 enrolled participants attended a 1-year follow-up visit. After 1 year, persistent seroconversion for pertussis toxin neutralising antibodies was seen in 38 (76%, 95% CI 64-88) participants in the aP(PTgen/FHA) group and 41 (81%, 70-92) in the TdaP(PTgen/FHA) group, but in only four (8%, 1-16) in the Tdap comparator group. Seroconversion rates for IgG antibodies against pertussis toxin and FHA were also greater in the aP(PTgen/FHA) group (82%, 95% CI 71-93 and 64%, 51-77, respectively) and TdaP(PTgen/FHA) group (75%, 63-87 and 56%, 42-70, respectively) than in the Tdap group (4%, 0-9, p<0·0001, and 28%, 16-41, p=0·0007, respectively). 13 serious adverse events were reported in 12 participants and all were judged to be unrelated to the study vaccines. Five pregnancies were reported during follow-up, none of which had any maternal or neonatal complications. INTERPRETATION: A monovalent and a combined recombinant acellular pertussis vaccine containing PTgen induced antibody responses that were greater and sustained for longer than those achieved with the Tdap comparator vaccine. New recombinant pertussis vaccines containing PTgen might offer new opportunities to limit pertussis resurgence and can be widely used, including in pregnant women. FUNDING: BioNet-Asia.


Assuntos
Anticorpos Antibacterianos/sangue , Antitoxinas/sangue , Toxina Pertussis/imunologia , Vacina contra Coqueluche/imunologia , Adolescente , Ásia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Toxina Pertussis/genética , Vacina contra Coqueluche/administração & dosagem , Vacina contra Coqueluche/efeitos adversos , Vacina contra Coqueluche/genética , Soroconversão , Método Simples-Cego , Fatores de Tempo , Vacinas Acelulares/administração & dosagem , Vacinas Acelulares/efeitos adversos , Vacinas Acelulares/genética , Vacinas Acelulares/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
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