RESUMO
OBJECTIVE: Management of cervical high-grade squamous intraepithelial lesions (HSILs), the immediate precursor of cervical cancer, consists largely of surgical treatment for women at higher risk for progression to cancer. The authors' objective was to describe the occurrence of cervical HSIL in the United States and various outcomes for women who received surgical treatment. METHODS: From a US commercial health insurer, a cohort of adult women with cervical HSIL diagnoses receiving surgical treatment within 3 months of diagnosis between January 2008 and September 2018 was identified. This cohort was followed for several outcomes, including cervical HSIL recurrence, human papillomavirus clearance, preterm birth, infection, and bleeding. RESULTS: The incidence rate of cervical HSIL declined from 2.34 (95% CI = 2.30-2.39) cases per 1,000 person-years in 2008 to 1.39 (95% CI = 1.35-1.43) cases per 1,000 person-years in 2014, remaining near that level through 2018. Among 65,527 women with cervical HSIL, 47,067 (72%) received surgical treatment within 3 months of diagnosis. Among the women receiving surgical treatment, cervical HSIL recurred in 6% of surgically treated women, whereas 45% of surgically treated women underwent subsequent virological testing that indicated human papillomavirus clearance. Preterm birth was observed in 5.9% by 5 years follow-up and bleeding and infection each at 2.2% by 7 days follow-up. CONCLUSIONS: From 2008 through 2018, the incidence of diagnosed cervical HSIL decreased for several years before stabilizing. Surgical treatment of HSIL may be beneficial in removing the precancerous lesion, but cervical HSIL may recur, and the surgery is associated with complications including preterm birth, infection, and bleeding.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Nascimento Prematuro , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Recém-Nascido , Adulto , Feminino , Humanos , Estados Unidos/epidemiologia , Displasia do Colo do Útero/patologia , Esfregaço Vaginal , Padrão de Cuidado , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/diagnóstico , Lesões Intraepiteliais Escamosas/epidemiologia , Lesões Intraepiteliais Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Resultado do Tratamento , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/diagnóstico , PapillomaviridaeRESUMO
VGX-3100 is an investigational DNA-based immunotherapy being developed as an alternative to surgery and ablation for cervical High-Grade Squamous Intraepithelial Lesion (HSIL) with the aim of preserving reproductive health while treating precancerous disease. Response durability up to 1.5 y following dosing is now reported.Histologic regression and HPV16 and/or HPV 18 (HPV16/18) clearance were previously demonstrated in a randomized, placebo-controlled, double-blind trial and reported for 6 months after the last dose of VGX-3100 or placebo. The presence of HPV16/18, Pap smear diagnoses, and immunogenicity longer-term responses were assessed at 18 months after the last dose.91% (32/35) VGX-3100-treated women, whose cervical HSIL regressed and avoided excision at 6 months following study treatment completion, had no detectable HPV16/18 at 18 months following treatment completion. These results were comparable to those for women who received placebo and then later underwent surgery. For VGX-3100 recipients who regressed at 6 months following study treatment completion and avoided excision during the trial, Pap testing showed no HSIL recurrence at 18 months following VGX-3100 treatment. VGX-3100-induced cellular immune responses specific for HPV 16/18 E6/E7 remained higher than for placebo control recipients at 18 months.In women with cervical HSIL who responded to VGX-3100 and were able to avoid surgery, clinical outcomes were comparable to the placebo control group which underwent conventional surgical treatment. These findings extend the understanding of the durability of the treatment effect of VGX-3100 up to 1.5 y and support that VGX-3100 could be used as an alternative to surgery.
Assuntos
Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Recidiva Local de Neoplasia , Papillomaviridae , Vacinas contra Papillomavirus , Vacinas de DNARESUMO
HPV remains the most common sexually transmitted disease worldwide, despite improvements in awareness, screening, prophylactic vaccination uptake, and surgical treatment. VGX-3100 is an immunotherapy that uses electroporation to introduce DNA encoding for modified HPV-16 and HPV-18, E6-and E7 proteins into myocytes to stimulate an effector T cell response. We now report immunogenicity and safety of VGX-3100 for a refrigeration-stable formulation, which improves patient-care setting usability. This multi-arm, double-blinded, randomized trial enrolled 235 healthy men and women to receive either a refrigerated (RF) or frozen formulation (FF) of VGX-3100. Three doses were administered intramuscularly with electroporation at 0, 4, and 12 weeks. Non-inferiority of RF to FF was assessed by comparing the proportion of subjects who achieved a ≥2-fold increase from baseline to Week 14 in Spot Forming Units/106 PMBCs using an interferon-γ enzyme-linked immunospot assay. There were no related SAEs. Injection site reactions were the most common adverse event (54%, RF; 66%, FF) the majority of which resolved within a few minutes following administration. The primary endpoint was met with 89.9% of RF recipients and 97.2% of FF recipients reaching a ≥2-fold rise in SFU/106 PBMC, 2 weeks following the last dose; RF was statistically non-inferior to FF (p = .022). A systemic, immunologic approach has the potential to fill a critical gap in the ability to treat men and women with high grade HPV diseases. These safety and immunogenicity data are supportive of the continued development of a refrigerated formulation of VGX-3100.
Assuntos
Leucócitos Mononucleares , Infecções por Papillomavirus , Anticorpos Antivirais , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Vacinação , Vacinas de DNA , Adulto JovemRESUMO
BACKGROUND: Patients with renal insufficiency are hyporesponsive to vaccination, including to hepatitis B vaccines. A manufacturing process modification for a hepatitis B vaccine (mpHBV) was studied in renal pre-dialysis and dialysis patients. METHODS: This randomized, open-label, multicenter, estimation study enrolled previously unvaccinated, HBV-seronegative adult dialysis and pre-dialysis patients (N=276, median age 72.0 years). At 0, 1, 6, and 8 months, group 1 received a 1 mL intramuscular dose of mpHBV (containing 40 µg HBsAg) as a single injection, while group 2 received a 1 mL intramuscular dose of a licensed hepatitis B vaccine as two injections (each containing 20 µg HBsAg; 40 µg HBsAg total). Serum antibody to HBsAg (anti-HBs) was measured predose 1, and 1 month postdose 3 and 4. Anti-HBs geometric mean concentration (GMC) and seroprotection rate (SPR, % of subjects with anti-HBs titer ≥10 mIU/mL) were estimated at months 7 and 9. RESULTS: For group 1, month 7 SPR was 48.5% (49/101, 95% CI: 38.4%, 58.7%); with an additional dose, month 9 SPR increased to 66.7% (66/99, 95% CI: 56.5%, 75.8%). For group 2, month 7 SPR was 57.7% (64/111, 95% CI: 47.9%, 67.0%); with an additional dose, month 9 SPR increased to 69.2% (72/104, 95% CI: 59.4%, 77.9%). group 1 GMCs at months 7 and 9 were 27.5 mIU/mL (95% CI: 15.7, 48.0) and 61.7 mIU/mL (95% CI: 34.2, 111.5), respectively. group 2 GMCs at months 7 and 9 were 48.7 mIU/mL (95% CI: 28.7, 82.7) and 115.8 mIU/mL (95% CI: 65.2, 205.5), respectively. There were 22 serious adverse events; none were considered related to study vaccine. CONCLUSIONS: Both formulations were immunogenic in this population but required more vaccinations to reach seroprotective levels than comparable regimens in healthy individuals, as expected. The relatively reduced SPRs seen in this population support the need for routine screening and re-dosing in this population.
Assuntos
Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Diálise Renal , Adulto , Idoso , Formação de Anticorpos , Método Duplo-Cego , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/efeitos adversos , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/uso terapêuticoRESUMO
BACKGROUND: A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. METHODS: Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5µg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. RESULTS: Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. CONCLUSIONS: The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Vacinação/efeitos adversos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Humanos , Recém-Nascido , Injeções Intramusculares , Masculino , Vacinação/métodos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologiaRESUMO
BACKGROUND: Generating protective immune responses in older adults (particularly ≥65 y) remains challenging for vaccines in general. This study examined the immune response engendered in older adults by RECOMBIVAX HB™ manufactured using a modified adjuvant (modified-process hepatitis B vaccine; mpHBV), RECOMBIVAX-HB™, and ENGERIX-B™. METHODS: Randomized, double-blind, multicenter study enrolled healthy, seronegative subjects (N=538) to receive mpHBV (10 µg hepatitis B surface antigen [HBsAg]), RECOMBIVAX-HB™ (10 µg HBsAg), or ENGERIX-B™ (20 µg HBsAg) at Day 1, Month 1, and Month 6. Prespecified analysis of subpopulations 50-64 y and ≥65 y was conducted. Serum antibody to HBsAg (anti-HBs) was measured Predose 1 and 1 mo Postdose 3. RESULTS: For subjects ≥50 y, seroprotection rates (SPR, anti-HBs titer ≥10 mIU/mL) were 75.7% (95% CI: 68.0,82.2) for mpHBV, 68.0% (95% CI: 59.8,75.5) for RECOMBIVAX HB™, and 84.0% (95% CI: 77.0,89.6) for ENGERIX-B™. For subjects 50-64 y, SPRs were 82.1% (95% CI: 73.8,88.7) for mpHBV, 77.4% (95% CI: 68.7,84.7) for RECOMBIVAX-HB™, and 88.5% (95% CI: 81.1,93.7) for ENGERIX-B™. For subjects ≥65 y, SPRs were 57.5% (95% CI: 40.9,73.0) for mpHBV, 34.4% (95% CI: 18.6,53.2) for RECOMBIVAX-HB™, and 67.7% (95% CI: 48.6,83.3) for ENGERIX-B™. There were 6 non-vaccine related serious adverse events reported. CONCLUSIONS: The majority of subjects ≥50 y old achieved seroprotection. The sub-population ≥65 y had lower vaccination responses than the 50-64 y sub-population. For subjects ≥65 y, mpHBV and ENGERIX-B™ groups achieved higher seroprotection rates than the RECOMBIVAX-HB group. The safety profile of mpHBV was consistent with the other groups.
Assuntos
Adjuvantes Imunológicos , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Vírus da Hepatite B/imunologia , Hepatite B/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/administração & dosagem , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologiaRESUMO
BACKGROUND: A hepatitis B vaccine was manufactured with a modified process (mpHBV) that incorporated double the usual amount of phosphate. Following a study in young adults, the mpHBV was evaluated in infants in a combination hepatitis B and Haemophilus influenzae B vaccine (mpHBV-Hib). METHODS: The mpHBV-Hib was compared with the licensed bivalent HBV-Hib vaccine Comvax™ for immunogenicity and safety. Both vaccines contained 5 µg/0.5 mL of hepatitis B surface antigen (HBsAg) and 7.5 µg/0.5 mL of PRP-OMPC (polyribosylribitol phosphate outer membrane protein complex). A total of 543 infants were randomized 1:1 to receive either vaccine at 2, 4 and 12 months of age. A pneumococcal conjugate vaccine (PCV) was given concomitantly. Immunogenicity was assessed at 1-month post-dose 3. RESULTS: Seroprotection rates [% subjects with anti-hepatitis B surface antigen antibody titers (anti-HBs) ≥10 mIU/mL)] were 100% and 99% for mpHBV-Hib and the licensed control (Comvax™), respectively. Anti-HBs geometric mean titers (GMTs) were 4204 (95% CI, 3411-5182) and 1683 (95% CI, 1350-2099) mIU/mL, respectively. Anti-PRP seroprotection rates (SPR) at ≥0.15 µg/mL and at ≥1.0 µg/mL were 97% and 94%, respectively, for mpHBV-Hib and 96% and 92%, respectively, for the control. Anti-PRP GMTs were 7.1 µg/mL for mpHBV-Hib and 8.0 µg/mL for the control. Reactogenicity of the two vaccines was similar. CONCLUSIONS: The mpHBV in combination with Hib and with co-administered PCV was highly immunogenic. The safety profile of mpHBV-Hib was comparable to the licensed control. Both the control and mpHBV-Hib met acceptability criteria for seroprotection rates to hepatitis B, with higher anti-HBs GMTs noted for mpHBV-Hib.
Assuntos
Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Imunização Secundária/métodos , Vacinação/métodos , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/imunologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/química , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/química , Humanos , Lactente , Masculino , Vacinas Pneumocócicas/administração & dosagem , Polissacarídeos Bacterianos/imunologia , Vacinas Conjugadas/administração & dosagemRESUMO
BACKGROUND: A modified process hepatitis B vaccine (mpHBV) uses higher phosphate content in the manufacturing process relative to the current product, Recombivax-HB. The higher phosphate is thought to improve antigen presentation, and thereby, increase antibody production. The mpHBV was previously shown to be well tolerated and immunogenic in adults. The current study tested a 2-, 4-, 6-month vaccination schedule and a higher dose formulation (10 µg mpHBV) in healthy infants. METHODS: In a randomized, double-blind study, healthy infants (N = 1718), approximately 2 months of age, received a 0.5-mL intramuscular dose of 5-µg mpHBV, Recombivax-HB (5 µg), 10-µg mpHBV, or Engerix-B (10 µg) at day 1, month 2, and month 4 (2, 4, 6 months of age). Serum antibody to hepatitis B surface antigen (anti-HBs) was analyzed at month 7. The geometric mean titer (GMT) and seroprotection rate (SPR; % subjects with anti-HBs titer ≥ 10 mIU/mL) were determined 1 month after the third dose. RESULTS: Month 7 SPRs were 99.3% (402/405, 95% confidence interval [CI]: 98.3, 100) in the 5 µg mpHBV group, 100.0% (398/398, 95% CI: 99.9, 100) in the 10 µg mpHBV group, 98.5% (400/406, 95% CI: 97.2, 99.8) in the Recombivax-HB group, and 99.5% (398/400, 95% CI: 98.7, 100) in the Engerix-B group. Month 7 GMTs (mIU/mL) were 748.2 (95% CI: 672.0, 833.1) in the 5 µg mpHBV group, 981.5 (95% CI: 891.0, 1081.2) in the 10 µg mpHBV group, 376.8 (95% CI: 331.4, 428.5) in the Recombivax-HB group, and 556.6 (95% CI: 491.8, 629.9) in the Engerix-B group. The percentages of subjects reporting injection-site or systemic adverse events were similar across the vaccination groups. CONCLUSIONS: All 4 hepatitis B vaccines elicited high anti-HBs SPRs. After dose 3, anti-HBs GMT were highest in the 10 µg mpHBV group, but did not meet the predefined criteria for superiority. All vaccines were well tolerated.
Assuntos
Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Imunização Secundária/métodos , Vacinação/métodos , Método Duplo-Cego , Feminino , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/química , Humanos , Lactente , Injeções Intramusculares , Masculino , Fosfatos/análiseRESUMO
The current recommended infant vaccination schedules require many injections at multiple sites, which increase stress for infants and parents and may create challenges to vaccination compliance. Therefore, combination vaccines, which reduce the number of injections at each medical visit, can be an essential method to improve compliance. The objective of this study was to assess the safety and immunogenicity of an investigational, liquid, hexavalent, pediatric vaccine at 2, 4, 6, and 12-14 months of age. In this multicenter, open-label controlled study, 756 infants were randomized in approximately equal numbers to receive 0.5mL intramuscular dose of diptheria-tetanus-pertussis-polio-Haemophilus influenzae type b+hepatitis B vaccine, or 1 of 3 double-blind investigational formulations. All formulations included a hepatitis B surface antigen (HBsAg) concentration of 10µg/0.5mL. The three hexavalent vaccine formulations used in this study contained either Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus toxoid [PRP-T, 12µg] or Neisseria meningitidis outer membrane protein complex [PRP-OPMC, 3µg or 6µg]): a minimum acceptable postdose 3 antibody response rate for each antigen was defined by the lower limit of a 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited vaccine-related injection-site reactions (pain, erythema, swelling) with increasing PRP-OMPC dose. No serious vaccine-related AEs were reported in the investigational groups. Both PRP-OMPC formulations met prespecified acceptability criteria for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and poliovirus. The PRP-T formulation met the acceptability criterion for antibody responses to all antigens other than PRP at postdose 3. Postdose 4 responses were adequate for all antigens in all formulations. All vaccine formulations were well-tolerated. Both PRP-OMPC formulations met prespecified immunogenicity criteria of PRP-OMPC evaluation.
Assuntos
Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Método Duplo-Cego , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Humanos , Lactente , Injeções Intramusculares , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem , Dermatopatias/induzido quimicamente , Dermatopatias/epidemiologia , Vacinas Combinadas , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologiaRESUMO
This open-label, randomized study challenged 4- to 8-year-old children from Spain (N = 1478) with a single dose of hepatitis B vaccine to estimate anamnestic responses. At the time of preimmunization, 15.9% to 51.2% of subjects had antibody values ≥10 mIU/mL. One month postimmunization, 91.6% to 97.3% of subjects had antibody titers ≥10 mIU/mL. There were no serious, vaccine-related, adverse experiences, and no discontinuations as a result of adverse experience.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Imunização Secundária , Criança , Pré-Escolar , Feminino , Vacinas contra Hepatite B/efeitos adversos , Humanos , Masculino , Espanha , Fatores de TempoRESUMO
Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12microg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3microg or 6microg]), and in hepatitis B surface antigen (HBsAg, 10microg or 15microg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity.
Assuntos
Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Química Farmacêutica , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Humanos , Imunização Secundária , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologiaRESUMO
BACKGROUND: Merck has developed a manufacturing process modification for RECOMBIVAX HB. Three lots of modified process hepatitis B vaccine (mpHBV) were studied in a randomized, blinded trial to demonstrate similarity of the three lots of mpHBV and noninferiority to RECOMBIVAX HB (control vaccine) with regard to immunogenicity. RESULTS: Month 7 SPRs for the mpHBV groups ranged from 97.8 to 98.9% (98.2% for the mpHBV groups combined). The seroprotection rate (SPR) for the control group was 98.5%. The estimated geometric mean titer (GMT) was 1761 mIU/mL for the mpHBV groups combined and 1108 mIU/mL for the control group. The GMT ratio (mpHBV/control) was 1.6 [95% confidence interval (CI): 1.2 to 2.1], indicating superiority of mpHBV compared with control. The percentages of subjects reporting any adverse experience (AE), injection-site AEs, or systemic AEs were similar across the four vaccination groups. There were no serious AEs. METHODS: Healthy 20-to 35-year-old subjects (N = 860) received a 1-mL intramuscular dose [10 mcg hepatitis B surface antigen (HBsAg)] of mpHBV from 1 of 3 lots or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed Predose 1 and 1 month Postdose 3 (Month 7) using a quantitative hepatitis B antibody assay (Ortho VITROS ECi assay). Anti-HBs GMTs and SPRs (% of subjects with an anti-HBs titer > or =10 mIU/mL) were compared at Month 7. After each dose, injection-site AEs and oral temperature were recorded for 5 days; systemic AEs were recorded for 15 days. CONCLUSIONS: The SPRs for the mpHBV groups and the control group were high; responses were consistent across the mpHBV groups. The mpHBV and control vaccines were generally well tolerated.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Adulto , Feminino , Humanos , Masculino , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto JovemRESUMO
RNA interference (RNAi) is an antiviral mechanism that is activated when double-stranded RNA is cleaved into fragments, called short interfering RNA (siRNA), that prime an inducible gene silencing enzyme complex. We applied RNAi against a herpes simplex virus type 1 (HSV-1) gene, glycoprotein E, which mediates cell-to-cell spread and immune evasion. In an in vitro model of infection, human keratinocytes were transfected with siRNA specific for glycoprotein E and then infected with wild-type HSV-1. RNAi-mediated gene silencing reproduced the small plaque phenotype of a gE-deletion mutant virus. The specificity of gene targeting was demonstrated by flow cytometry and Northern blot analyses. Exogenous siRNA can suppress HSV-1 glycoprotein E expression and function during active infection in vitro through RNAi. This work establishes RNAi as a genetic tool for the study of HSV and provides a foundation for development of RNAi as a novel antiviral therapy.