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1.
CMAJ Open ; 11(1): E24-E32, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36627129

RESUMO

BACKGROUND: The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. METHODS: We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. RESULTS: All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. INTERPRETATION: At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.


Assuntos
Vírus da Hepatite B , Hepatite B , Adolescente , Lactente , Criança , Humanos , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Análise Custo-Benefício , Ontário/epidemiologia , Vacinas contra Hepatite B , Vacinas Combinadas , Vacinação
2.
Viruses ; 15(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680259

RESUMO

Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with the goal of reducing clinical recurrences and recurrent virus shedding. In our previous work, we evaluated recombinant adenovirus-based vaccines, including rAd-gD2ΔUL25, rAd-ΔUL25, and rAd-gD2, for their potency as prophylactic vaccines. In this study, we evaluated these three vaccines as therapeutic vaccines against acute and recurrent diseases in intravaginal challenged guinea pigs. Compared with the control groups, the recombinant vaccine rAd-gD2ΔUL25 induced a higher titer of the binding antibody, and rAd-gD2 + rAd-ΔUL25 induced a higher titer of the neutralizing antibody. Both rAd-gD2ΔUL25 and rAd-gD2 + rAd-ΔUL25 vaccines significantly enhanced the survival rate by 50% compared to rAd-gD2 and reduced viral replication in the genital tract and recurrent genital skin disease. Our findings provide a new perspective for HSV-2 therapeutic vaccine research and provide a new technique to curtail the increasing spread of HSV-2.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Herpes Genital , Vacinas contra o Vírus do Herpes Simples , Cobaias , Animais , Herpesvirus Humano 2/genética , Adenoviridae/genética , Proteínas do Envelope Viral/genética , Herpes Genital/prevenção & controle , Vacinas Sintéticas/genética , Anticorpos Antivirais
3.
MMWR Morb Mortal Wkly Rep ; 72(2): 33-38, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36634013

RESUMO

Millions of young children are vaccinated safely in the United States each year against a variety of potentially dangerous infectious diseases (1). The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination against 14 diseases during the first 24 months of life* (2). This report describes vaccination coverage by age 24 months using data from the National Immunization Survey-Child (NIS-Child).† Compared with coverage among children born during 2016-2017, coverage among children born during 2018-2019 increased for a majority of recommended vaccines. Coverage was >90% for ≥3 doses of poliovirus vaccine (93.4%), ≥3 doses of hepatitis B vaccine (HepB) (92.7%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.6%), and ≥1 dose of varicella vaccine (VAR) (91.1%); coverage was lowest for ≥2 doses of hepatitis A vaccine (HepA) (47.3%). Vaccination coverage overall was similar or higher among children reaching age 24 months during March 2020 or later (during the COVID-19 pandemic) than among those reaching age 24 months before March 2020 (prepandemic); however, coverage with the combined 7-vaccine series§ among children living below the federal poverty level or in rural areas decreased by 4-5 percentage points during the pandemic (3). Among children born during 2018-2019, coverage disparities were observed by race and ethnicity, poverty status, health insurance status, and Metropolitan Statistical Area (MSA) residence. Coverage was typically higher among privately insured children than among children with other insurance or no insurance. Persistent disparities by health insurance status indicate the need to improve access to vaccines through the Vaccines for Children (VFC) program.¶ Providers should review children's histories and recommend needed vaccinations during every clinical encounter and address parental hesitancy to help reduce disparities and ensure that all children are protected from vaccine-preventable diseases.


Assuntos
COVID-19 , Cobertura Vacinal , Estados Unidos/epidemiologia , Humanos , Lactente , Pré-Escolar , Pandemias , Esquemas de Imunização , Vacinação , Vacina contra Varicela , Vacinas Combinadas
5.
Vaccine ; 41(3): 795-804, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36528443

RESUMO

BACKGROUND: Vaccination during pregnancy with tetanus, diphtheria, acellular pertussis (aP) (Tdap) antigens is important for early protection of newborn infants against pertussis, particularly for preterm infants. This study evaluated the effect of Tdap vaccination during pregnancy on the immunogenicity of a diphtheria (D), tetanus (T), aP, inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b (PRP âˆ¼ T) vaccine in term and preterm populations. METHODS: A prospective, observational study (NCT02511327) recruited women and their infants based on delivery (term or preterm) and vaccination status (vaccinated with a Tdap vaccine [Boostrix™, GlaxoSmithKline] during pregnancy or not vaccinated in the last 5 years). All infants received licensed DTaP-IPV-HB-PRP âˆ¼ T (Hexyon™, Sanofi) (8, 12, 16 week primary series and booster at 13 months of age [preterm infants] or 15 months of age [term infants]). Immunogenicity was evaluated using validated assays. Data were pooled into term (N = 127) and preterm infants (N = 105), and infants of women who received a Tdap vaccine during pregnancy (N = 199) or not (N = 33). RESULTS: Before primary vaccination, antibody levels were higher for term than preterm infants for anti-D, anti-polio 1, 2, 3, anti-PT, anti-FHA, and anti-PRP, and similar for anti-HBs and anti-T. At this time, infants of Tdap-vaccinated women had higher anti-D, anti-T, anti-PT, anti-FHA, and anti-PRP antibody levels than infants of Tdap-unvaccinated women; anti-HBs and anti-polio antibody levels were similar in both groups. Post-primary, pre-booster, and post-booster, there were only small differences in seroprotection rates (anti-D, anti-T, anti-polio 1, 2, 3, anti-HBs, anti-PRP) and seroconversion rates (anti-PT, anti-FHA), except for anti-HBs ≥ 10 mIU/mL and anti-PRP ≥ 0.15 µg/mL post-primary vaccination (higher for term [98.31 % and 90.91 %, respectively] versus preterm infants [89.80 % and 79.41 %, respectively]). CONCLUSIONS: These data support the use of DTaP-IPV-HB-PRP âˆ¼ T vaccine for primary and booster vaccination in term and preterm born infants and in infants born to Tdap-vaccinated or Tdap-unvaccinated women.


Assuntos
Difteria , Vacinas Anti-Haemophilus , Poliomielite , Tétano , Coqueluche , Lactente , Gravidez , Humanos , Recém-Nascido , Feminino , Tétano/prevenção & controle , Vacinas Combinadas , Difteria/prevenção & controle , Coqueluche/prevenção & controle , Vacinas contra Hepatite B , Estudos Prospectivos , Vacina Antipólio de Vírus Inativado , Imunização Secundária , Recém-Nascido Prematuro , Anticorpos Antibacterianos , Vacinação , Corynebacterium , Anticorpos Anti-Hepatite B , Vacina contra Difteria, Tétano e Coqueluche
6.
ACS Nano ; 17(1): 760-774, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36520665

RESUMO

Tumor vaccines have been showing a relatively weak response rate in cancer patients, while deficiencies in delivery efficiency to dendritic cells (DCs), as well as DC-intrinsic immunosuppressive signals, contribute to a great extent. In this work, we report an implantable blood clot loaded with liposomes-protamine-hyaluronic acid nanoparticles (LPH NPs) containing vaccine (LPH-vaccine) and LPH NPs containing siRNA (LPH-siRNA) for synergistic DC recruitment and activation. The subcutaneously implanted blood clot scaffold can recruit abundant immune cells, particularly DCs, to form a DC-rich environment in vivo. Within the scaffold, LPH-vaccine effectively delivers antigens and adjuvants to the recruited DCs and induces the maturation of DCs. More importantly, LPH-siRNA that targets programmed death-ligand 1 (PD-L1) and T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) can reduce immunosuppressive signals in mature DCs and prevent the DCs from expressing a regulatory program in the scaffold. The activated DCs correlate with an improved magnitude and efficacy of T cell priming, resulting in the production of tumor antigen-specific T cells in multiple mouse models. Our strategy can also be used for patient-tailored therapy by change of tumor neoantigens, suggesting a promising strategy for cancer therapy in the clinic.


Assuntos
Vacinas Anticâncer , Neoplasias , Trombose , Animais , Camundongos , RNA Interferente Pequeno/genética , Lipossomos , Antígeno B7-H1/genética , Receptor Celular 2 do Vírus da Hepatite A , Imunoterapia/métodos , Neoplasias/terapia , Células Dendríticas
7.
J Med Virol ; 95(1): e28434, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36571260

RESUMO

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46-0.93), cancer (OR: 0.65; 95% CI: 0.42-0.99), and diabetes (OR: 0.50; 95% CI: 0.28-0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11-0.76), cancer (OR: 0.38; 95% CI: 0.23-0.62), and diabetes (OR: 0.37; 95% CI: 0.20-0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Doença Crônica , China , Anticorpos Neutralizantes , Imunoglobulina G , Vacinação , Anticorpos Antivirais
8.
Expert Rev Vaccines ; 22(1): 104-117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36545777

RESUMO

INTRODUCTION: Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b. AREAS COVERED: To evaluate the immunogenicity and reactogenicity (safety) of Hexaxim (Hexyon, Hexacima) in primary and booster vaccine schedules; long-term antibody persistence; concomitant use with other childhood vaccines and use in immunocompromised infants. Hexaxim was found to be noninferior to other licensed hexavalent vaccines, being highly immunogenic for all toxoids/antigens and with an acceptable safety profile. It can be administered concomitantly with other childhood vaccines. Hexaxim can be given as a booster for infants primed with Infanrix Hexa and given in a pentavalent-hexavalent-pentavalent series. Hexaxim elicits a similar immune response and safety profile in human immunodeficiency virus (HIV) positive infants. It has the benefit of being a ready-to-use liquid formulation, minimizing dosage errors and preparation time. EXPERT OPINION: Hexaxim has an acceptable safety profile and provides immunity against all six targeted diseases. It is an acceptable alternative to other hexavalent vaccines on the market. Further studies are required on the use of immunocompromised patients as well as the antibody persistence of each of the vaccine components.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Lactente , Humanos , Criança , Imunização Secundária , Esquemas de Imunização , Vacina Antipólio de Vírus Inativado , Vacinas contra Hepatite B , Vacinas Combinadas , Anticorpos Antibacterianos
10.
BMC Public Health ; 22(1): 2259, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463130

RESUMO

BACKGROUND: Immunization is one of the most important public health interventions for reducing morbidity and mortality in children. However, factors contributing to low immunization coverage are not fully understood in the Lao People's Democratic Republic (Lao PDR). Therefore, this study aimed to identify factors associated with full immunization coverage among children between 12 and 35 months, providing up-to-date information for immunization programs in Lao PDR. METHODS: We analyzed the subpopulation of a nationwide cross-sectional survey using a multistage cluster sampling procedure to evaluate the measles and rubella seroepidemiology. In addition, we categorized children aged between 12 and 35 months into two groups: "fully immunized" children with a birth dose of Bacillus Calmette and Guérin vaccine, hepatitis B vaccine (Hep B), one and three doses for the measles-containing vaccine (MCV) and pentavalent vaccine and pneumococcal conjugate vaccine (PCV) and "partially immunized" children who missed any dose of vaccine. Immunization coverage was calculated as the ratio of "fully immunized" to the total. We compared the groups' demographic characteristics and health service utilization as independent variables. Multivariate logistic regression was used to assess the relationship between immunization coverage, various demographic factors, and health service utilization. RESULTS: Overall, 256 of the 416 targeted pairs were included in the analysis. In total, 67.6% of the children were fully immunized. Childbirth at hospitals or health facilities (adjusted odds ratio: 9.75, 95% confidence interval: 5.72-16.62, p < 0.001) was the predictor of full immunization coverage. The 83 children in the partially immunized groups were attributed to Hep B at birth (46, 55.4%), three doses of PCV (34, 41.0%), and the first dose of the MCV (27, 32.5%). CONCLUSION: Our study elucidated that the immunization status among children aged between 12 and 35 months in Lao PDR is satisfactory in improving access to healthcare by strengthening communication with residents regarding health service utilization, and expanding mobile outreach services may play a pivotal role in this endeavor. Further research is warranted to evaluate efforts to increase immunization coverage and target populations with limited access to healthcare.


Assuntos
Sarampo , Vacinas Virais , Recém-Nascido , Criança , Gravidez , Feminino , Humanos , Lactente , Pré-Escolar , Cobertura Vacinal , Estudos Transversais , Laos/epidemiologia , Estudos Soroepidemiológicos , Vacina contra Sarampo , Vacinas Conjugadas
11.
BMC Nephrol ; 23(1): 400, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36513992

RESUMO

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia. It is related to severe deficiency in ADAMTS13, which is usually acquired via ADAMTS13 autoantibodies or inherited via mutations of the ADAMTS13 gene. The etiology of acquired TTP including HIV infection, pregnancy, autoimmune disease, organ transplantation, drugs, malignancy and so on. Here, we firstly reported a patient diagnosed as acquired TTP after pegylated interferon therapy for hepatitis B and COVID-19 vaccination. CASE PRESENTATION: A 36-year-old male attended to our unit with a five-day history of intermittent hematuria and progressive fatigue on January 5th, 2022. He had a 13 years history of hepatitis B infection and undergone pegylated interferon treatment (which was paused for two months because of COVID-19 vaccination) for nearly 3 years. Laboratory evaluation revealed a haemoglobin level of 61 g/L, platelet count of 11 × 109/L, lactate dehydrogenase 2133 U/L. The direct and indirect Coombs test were both negative. On a peripheral blood smear, there were about 18.8% schistocytes. Meanwhile, the results of ADAMTS 13 activity and antibody were < 5% and 181.34 ng/ml (131.25-646.5), respectively CONCLUSION: This case firstly reported the rare complication of TTP after pegylated interferon treatment for hepatitis B and COVID-19 vaccine injection. This unique sign warrants more attention as an early cue of diagnosis of TTP and be aware of the rarity adverse effect of interferon therapy and COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Infecções por HIV , Hepatite B , Púrpura Trombocitopênica Trombótica , Adulto , Feminino , Humanos , Masculino , Gravidez , Vacinas contra COVID-19/efeitos adversos , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Interferons , Polietilenoglicóis/efeitos adversos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia
12.
Int J Mol Sci ; 23(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36555153

RESUMO

Since the beginning of the COVID-19 pandemic, considerable efforts have been made to develop protective vaccines against SARS-CoV-2 infection. However, immunity tends to decline within a few months, and new virus variants are emerging with increased transmissibility and capacity to evade natural or vaccine-acquired immunity. Therefore, new robust strategies are needed to combat SARS-CoV-2 infection. The viral spike composed of S1 and S2 subunits mediates viral attachment and membrane fusion to infect the host cell. In this process, interaction between the highly conserved heptad repeat 1 and 2 regions (HR1 and HR2) of S2 is crucial and for this reason; these regions are promising targets to fight SARS-CoV-2. Here, we describe the design and characterization of chimeric proteins that structurally imitate the S2 HR1 region in a trimeric coiled-coil conformation. We biophysically characterized the proteins and determined their capacity to bind the HR2 region, as well as their inhibitory activity of SARS-CoV-2 infection in vitro. HR1 mimetic proteins showed conformational heterogeneity and a propensity to form oligomers. Moreover, their structure is composed of subdomains with varied stability. Interestingly, the full HR1 proteins showed high affinity for HR2-derived peptides and SARS-CoV-2 inhibitory activity, whereas smaller proteins mimicking HR1 subdomains had a decreased affinity for their complementary HR2 region and did not inhibit the virus. The results provide insight into effective strategies to create mimetic proteins with broad inhibitory activity and therapeutic potential against SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Proteínas do Envelope Viral/química , Glicoproteínas de Membrana/metabolismo , Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/metabolismo , Pandemias , Vacinas contra COVID-19 , Proteínas Recombinantes de Fusão
13.
Hum Vaccin Immunother ; 18(7): 2160158, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36576263

RESUMO

The DTacP-sIPV-Hib combination vaccine can replace the single-component acellular pertussis, diphtheria, tetanus, polio, and Haemophilus influenzae type B vaccines. In this study, we evaluated the safety and immunogenicity of a newly developed DTacP-sIPV-Hib combination vaccine in animal models. We used 40 mice and 46 cynomolgus monkeys to evaluate acute and long-term toxicity. Thirty-six guinea pigs were used for sensitization assessment. For immunogenicity assessment, 50 NIH mice and 50 rats were equally randomized to receive 3 doses of 3 different batches of the tested vaccine at an interval of 21 d, or physiological saline solution (0.5 mL). Orbital blood was collected at an interval of 21 d post inoculation to detect related antibody titers or neutralizing antibody titers against poliovirus. Gross autopsy and histopathological examination revealed no abnormal toxicity or irritation in mice and cynomolgus monkeys. Sensitization assessment in guinea pigs indicated the lack of evident allergic symptoms in the high- and low-dose vaccine groups within 30 min after repeated stimulation. The DTacP-sIPV-Hib combination vaccine induced significant immune responses in mice, rats, and cynomolgus monkeys, with 100% seroconversion rates after 3 doses. The DTacP-sIPV-Hib combination vaccine is safe and immunogenic in animal models. Three doses of the vaccine elicited satisfactory antibody responses in mice, rats, and cynomolgus monkeys.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Vacinas Anti-Haemophilus , Vacina Antipólio de Vírus Inativado , Vacinas Combinadas , Animais , Cobaias , Camundongos , Ratos , Anticorpos Antibacterianos , Haemophilus influenzae tipo b , Vacinas contra Hepatite B , Macaca fascicularis , Modelos Animais , Vacinas Combinadas/efeitos adversos
14.
Rinsho Ketsueki ; 63(11): 1513-1519, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36476790

RESUMO

A 34-year-old man with no medical history presented with fever 4 days after receiving the first dose of mRNA-1273 coronavirus disease 2019 (COVID-19) vaccine. He had no prior clinical evidence of severe acute respiratory syndrome coronavirus 2 infection and was negative for serial polymerase chain reaction testing. Ten days after vaccination, he was referred to our hospital because of no response to antibiotics and the emergence of neutropenia, thrombocytopenia, and liver dysfunction. Blood tests also showed elevated serum ferritin and plasma soluble interleukin-2 receptors. Serological and PCR testing excluded active infections of cytomegalovirus, Epstein-Barr virus, and hepatitis viruses. Blood culture yielded no growth. Computed tomography revealed mild hepatosplenomegaly and porta hepatis lymphadenopathy but no focus on infection. Bone marrow aspiration demonstrated hemophagocytosis but no infiltrating lymphoma cells. Immediately, 2-mg/kg intravenous methylprednisolone was commenced based on the presumptive diagnosis of hemophagocytic lymphohistiocytosis (HLH), leading to the rapid and durable improvement of his symptoms and laboratory data. Later, without other causes triggering hemophagocytosis, and with the close link between vaccination and disease onset, the final diagnosis of vaccination-induced secondary HLH was made. HLH after COVID-19 vaccination, though extremely rare, can occur regardless of the vaccine type. Therefore, clinicians should recognize and deal with this occasionally fatal adverse event.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Humanos , Adulto , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Vacina de mRNA-1273 contra 2019-nCoV , Herpesvirus Humano 4
15.
Front Immunol ; 13: 1035073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505482

RESUMO

Vaccination is one of the most vigorous ways to intervene in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Cases of autoimmune hepatitis (AIH) after coronavirus disease (COVID-19) vaccination have been increasingly reported. Twenty-seven cases of AIH are summarized in this study, providing emerging evidence of autoimmune reactions in response to various COVID-19 vaccines, including in patients with special disease backgrounds such as primary sclerosing cholangitis (PSC), liver transplantation, and previous hepatitis C virus (HCV) treatment. Molecular mimicry, adjuvants, epitope spreading, bystander activation, X chromosome, and sceptical hepatotropism of SARS-CoV-2 may account for, to some extent, such autoimmune phenomena. Immunosuppressive corticosteroids perform well with or without azathioprine in such post-COVID-19-vaccination AIH. However, determination of the exact mechanism and establishment of causality require further confirmation.


Assuntos
COVID-19 , Hepatite Autoimune , Humanos , Hepatite Autoimune/etiologia , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinação/efeitos adversos
16.
Viruses ; 14(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36560782

RESUMO

Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hepatopatias , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Cirrose Hepática , SARS-CoV-2 , Vacinação/efeitos adversos
17.
Nat Commun ; 13(1): 7271, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434005

RESUMO

Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization.


Assuntos
Hepatite C , Nanopartículas , Vacinas , Humanos , Hepacivirus/genética , Anticorpos Neutralizantes , Anticorpos Amplamente Neutralizantes , Proteínas do Envelope Viral , Anticorpos Anti-Hepatite C , Glicoproteínas
18.
Am Fam Physician ; 106(5): 534-542, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36379499

RESUMO

Adult vaccination rates are low in the United States, despite clear benefits for reducing morbidity and mortality. Vaccine science is evolving rapidly, and family physicians must maintain familiarity with the most recent guidelines. The recommended adult immunization schedule is updated annually by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention. All eligible patients should receive SARS-CoV-2 vaccines according to the current guidelines. Adults without contraindications should also receive an annual influenza vaccine. Hepatitis A vaccine is recommended for adults with specific risk factors. All pregnant patients, adults younger than 60 years, and those 60 years and older who have risk factors should receive a hepatitis B vaccine. A 15- or 20-valent pneumococcal conjugate vaccine is recommended for all patients who are 65 years and older. Patients who receive 15-valent pneumococcal conjugate vaccine should receive a dose of 23-valent pneumococcal polysaccharide vaccine one year later. Adults 19 to 64 years of age should receive a pneumococcal vaccination if they have medical risk factors. A single dose of measles, mumps, and rubella vaccine is recommended for adults without presumptive immunity, and additional doses are recommended for patients with HIV and postdelivery for pregnant patients who are not immune to rubella. A tetanus and diphtheria toxoids booster is recommended every 10 years. For pregnant patients and those in close contact with young infants, a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine should be administered. The human papillomavirus vaccine is recommended for all people through 26 years of age. Herpes zoster vaccine is indicated for all adults 50 years and older. .


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Lactente , Gravidez , Feminino , Humanos , Estados Unidos , Vacinas Conjugadas , SARS-CoV-2 , Esquemas de Imunização , Vacinação
19.
Nat Commun ; 13(1): 6866, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369243

RESUMO

The effectiveness of a 3rd dose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3rd dose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively. The 4th dose recalls waned immunity while having distinct effects on humoral responses to different antigens. The peak antibody response to the RBD induced by the 4th dose is inferior to that after the 3rd dose, whereas responses to the N-terminal domain (NTD) of spike protein are further strengthened significantly. Accordingly, the 4th dose further elevates the peak level of NAbs against ancestral SARS-CoV-2 and Omicron BA.2, but not BA.1 which has more NTD mutations. No severe adverse events related to vaccination are recorded during the trial. Here, we show that redistribution of immune focus after repeated vaccinations may modulate cross-protective immune responses against different VOCs.


Assuntos
COVID-19 , Vacinas Virais , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Imunidade Humoral , Glicoproteínas de Membrana/genética , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas de Produtos Inativados , Proteínas do Envelope Viral
20.
Cell Mol Immunol ; 19(12): 1347-1360, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36369367

RESUMO

Chronic hepatitis B (CHB) infection remains a serious public health problem worldwide; however, the relationship between cholesterol levels and CHB remains unclear. We isolated peripheral blood mononuclear cells from healthy blood donors and CHB patients to analyze free cholesterol levels, lipid raft formation, and cholesterol metabolism-related pathways. Hepatitis B virus (HBV)-carrier mice were generated and used to confirm changes in cholesterol metabolism and cell-surface lipid raft formation in dendritic cells (DCs) in the context of CHB. Additionally, HBV-carrier mice were immunized with a recombinant HBV vaccine (rHBVvac) combined with lipophilic statins and evaluated for vaccine efficacy against HBV. Serum samples were analyzed for HBsAg, anti-HBs, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg. CHB reduced free cholesterol levels and suppressed lipid raft formation on DCs in patients with CHB and HBV-carrier mice, whereas administration of lipophilic statins promoted free cholesterol accumulation and restored lipid rafts on DCs accompanied by an enhanced antigen-presentation ability in vitro and in vivo. Cholesterol accumulation on DCs improved the rHBVvac-mediated elimination of serum HBV DNA and intrahepatic HBV DNA, HBV RNA, and HBcAg and promoted the rHBVvac-mediated generation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells, induction of the development of memory responses against HBV reinfection, and seroconversion from HBsAg to anti-HBs. The results demonstrated the important role of cholesterol levels in DC dysfunction during CHB, suggesting that strategies to increase cholesterol accumulation on DCs might enhance therapeutic vaccine efficacy against HBV and support development toward clinical CHB treatment.


Assuntos
Hepatite B Crônica , Hepatite B , Inibidores de Hidroximetilglutaril-CoA Redutases , Vacinas , Camundongos , Animais , Antígenos de Superfície da Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B/uso terapêutico , DNA Viral , Leucócitos Mononucleares , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vírus da Hepatite B , Anticorpos Anti-Hepatite B , Células Dendríticas , Colesterol/uso terapêutico , RNA
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