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1.
Vaccines (Basel) ; 12(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38793744

RESUMO

Since the beginning of the COVID-19 pandemic, different viral vector-based and mRNA vaccines directed against the SARS-CoV-2 "S" spike glycoprotein have been developed and have shown a good profile in terms of safety and efficacy. Nevertheless, an unbiased comparison of vaccination efficiency, including post-vaccination neutralizing activity, between the different vaccines remains largely unavailable. This study aimed to compare the efficacy of one mRNA (BNT162b2) and two non-replicating adenoviral vector vaccines (ChAdOx1 nCoV-19 and Sputnik V) in a cohort of 1120 vaccinated Palestinian individuals who received vaccines on an availability basis and which displayed a unique diversity of genetic characteristics. We assessed the level of anti-S antibodies and further determined the antibody neutralizing activity in 261 of those individuals vaccinated with BNT162b2a (121), ChAdOx1 (72) or Sputnik V (68). Our results showed no significant difference in the distribution of serum-neutralizing activity or S-antibody serum levels for the three groups of vaccines, proving equivalence in efficacy for the three vaccines under real-life conditions. In addition, none of the eight demographic parameters tested had an influence on vaccination efficacy. Regardless of the vaccine type, the vaccination campaign ultimately played a pivotal role in significantly reducing the morbidity and mortality associated with COVID-19 in Palestine.

2.
Regul Toxicol Pharmacol ; 149: 105617, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38561146

RESUMO

Accumulating evidence has shown that the abnormal toxicity test (ATT) is not suitable as a quality control batch release test for biologics and vaccines. The purpose of the current study was to explore the optimal ATT experimental design for an adenoviral vector-based vaccine product to avoid false positive results following the standard test conditions stipulated in the Pharmacopoeias. ATT were conducted in both mice and guinea pigs based on methods in Pharmacopeias, with modifications to assess effects of dose volume and amount of virus particles (VPs). The results showed intraperitoneal (IP) dosing at human relevant dose and volume (i.e., VPs), as required by pharmacopeia study design, resulted in false positive findings not associated with extraneous contaminants of a product. Considering many gene therapy products use adeno associated virus as the platform for transgene delivery, data from this study are highly relevant in providing convincing evidence to show the ATT is inappropriate as batch release test for biologics, vaccine and gene therapy products. In conclusion, ATT, which requires unnecessary animal usage and competes for resources which otherwise can be spent on innovative medicine research, should be deleted permanently as batch release test by regulatory authorities around the world.


Assuntos
Vetores Genéticos , Testes de Toxicidade , Animais , Cobaias , Testes de Toxicidade/métodos , Camundongos , Reações Falso-Positivas , Feminino , Adenoviridae/genética , Masculino , Vacinas
3.
Int Immunopharmacol ; 130: 111710, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38394888

RESUMO

Influenza virus is a kind of virus that poses several hazards of animal and human health. Therefore, it is important to develop an effective vaccine to prevent influenza. To this end we successfully packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP. The effect of rAd-NP-M2e-GFP on the activation of dendritic cell (DC) in vitro and in vivo was detected by intranasal immunization. The results showed that rAd-NP-M2e-GFP promoted the activation of DC in vitro and in vivo. After the primary immunization and booster immunization of mice through the nasal immune way, the results showed that rAd-NP-M2e-GFP induced enhanced local mucosal-specific T cell responses, increased the content of SIgA in broncho alveolar lavage fluids (BALF) and triggered the differentiation of B cells in the germinal center. It is proved that rAd-NP-M2e-GFP can significantly elicit mucosal immunity and systemic immune response. In addition, rAd-NP-M2e-GFP could effectively protect mice after H1N1 influenza virus challenge. To lay the foundation and provide reference for further development of influenza virus mucosal vaccine in the future.


Assuntos
Vacinas contra Adenovirus , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Camundongos , Humanos , Adenoviridae/genética , Imunização , Vacinas Sintéticas , Imunidade nas Mucosas , Camundongos Endogâmicos BALB C , Anticorpos Antivirais
4.
Antiviral Res ; 223: 105825, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311297

RESUMO

Feline coronavirus (FCoV) is an unsegmented, single-stranded RNA virus belonging to the Alphacoronavirus genus. It can cause fatal feline infectious peritonitis (FIP) in cats of any ages. Currently, there are no effective prevention and control measures to against FCoV. In this study, we developed a recombinant adenovirus vaccine, AD5-N, based on the nucleocapsid(N) protein of FCoV. The immunogenicity of AD5-N was evaluated through intramuscular immunization in 6-week-old Balb/c mice and 9-12 months old cats. Compared to the control group, AD5-N specifically induced a significant increase in IgG and SIgA levels in the vaccinated mice. Furthermore, AD5-N not only effectively promoted strong cellular immune responses in cats but also induced high levels of specific SIgA, effectively helping cats resist FCoV infection. Our findings suggest that adenovirus vector vaccines based on the N gene have the potential to become candidate vaccines for the prevention and control of FCoV infection.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Infecções por Coronavirus , Coronavirus Felino , Vacinas , Gatos , Animais , Camundongos , Adenoviridae/genética , Coronavirus Felino/genética , Imunoglobulina A Secretora , Camundongos Endogâmicos BALB C , Imunidade
5.
J Immunotoxicol ; 20(1): 2176952, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36788724

RESUMO

Cytotoxic T-lymphocytes (CTL) are a subset of T-cells that play a critical role in protecting against intracellular infections and cancer, and have the ability to identify and kill infected or transformed cells expressing non-self peptides associated with major histocompatibility (MHC) Class I molecules. Conversely, aberrant CTL activity can contribute to immune-related pathology under conditions of overwhelming infection or autoimmunity. Disease-modifying therapeutics can have unintended effects on CTL, and a growing number of therapeutics are intended to either suppress or enhance CTL or their functions. The susceptibility of CTL to unintended effects from common therapeutic modalities underscores the need for a better understanding of the impact that such therapies have on CTL function and the associated safety implications. While there are reliable ways of quantifying CTL, notably via flow cytometric analysis of specific CTL markers, it has been a greater challenge to implement fit-for-purpose methods measuring CTL function in the context of safety studies of therapeutics. This review focuses on methods for measuring CTL responses in the context of drug safety and pharmacology testing, with the goals of informing the reader about current approaches, evaluating their pros and cons, and providing perspectives on the utility of these approaches for safety evaluation.


Assuntos
Neoplasias , Linfócitos T Citotóxicos , Animais , Primatas , Neoplasias/terapia , Citotoxicidade Imunológica
6.
Viruses ; 15(2)2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36851544

RESUMO

Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 110 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, are stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. This review aimed to highlight the HAdV variability and the pandemic potential that a HAdV3 and 7 recombinant could have considering the aggressive outbreaks produced in health facilities. Herein, we described the characteristics of HAdV, from the infection to treatment, vaccine development, and the evaluation of the social determinants of health associated with HAdV, suggesting the necessary measures for future sanitary control to prevent disasters such as the SARS-CoV-2 pandemic, with an emphasis on the use of recombinant AdV vaccines to control other potential pandemics.


Assuntos
Adenovírus Humanos , COVID-19 , Humanos , Criança , Adenoviridae , Pandemias/prevenção & controle , Amigos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2/genética , Adenovírus Humanos/genética
7.
Fertil Steril ; 119(4): 618-623, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36539057

RESUMO

OBJECTIVE: To assess whether vaccination or the type of vaccine against SARS-CoV-2 affects ovarian function in an assisted reproduction treatment. DESIGN: A retrospective and observational study. SETTING: University-affiliated private in vitro fertilization (IVF) center. PATIENT(S): Five hundred one patients who had received the complete vaccination schedule. INTERVENTION(S): Treatment before and after vaccination. MAIN OUTCOME MEASURE(S): Parameters for both reproductive outcomes and IVF results in patients vaccinated RESULT(S): We included 510 patients, distributed as follows: 13.5% (n = 69) received a viral vector vaccine, either the adenovirus serotype 26 vector vaccine (Ad26.CoV2.S; Janssen; n = 31) or the chimpanzee adenovirus vector vaccine (ChAdOx; AstraZeneca; n = 38). The remaining 86.5% (n = 441) received an messenger RNA vaccine from either Pfizer-BioNTech (n = 336) or Moderna (n = 105). Sample size for the unexposed women was n = 1190. No differences were found in any of the evaluated parameters for both reproductive outcomes and IVF results in patients vaccinated with any adenovirus or messenger RNA vaccine. When we compared the results after vaccination with different types of vaccines between the exposed and unexposed groups, and similar results were obtained in the days of stimulation or the doses of administered follicle stimulating hormone. Finally, the numbers of oocytes were as follows: Johnson & Johnson (9.2 ± 2.6), AstraZeneca (7.7 ± 1.2), Moderna (11.3 ± 1.8), Pfizer (12.6 ± 1.0), and the unvaccinated group (10.2 ± 1.5), P=0.057. CONCLUSION(S): These early results suggest no measurable detrimental effect on reproductive outcomes, regardless of the type of vaccine received.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Fertilização in vitro , Ovário , Feminino , Humanos , Ad26COVS1 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Reprodução , Estudos Retrospectivos , RNA Mensageiro , SARS-CoV-2 , Vacinação/efeitos adversos , Ovário/efeitos dos fármacos , ChAdOx1 nCoV-19
8.
Vaccines (Basel) ; 12(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38250854

RESUMO

Newcastle disease (ND) remains a critical disease affecting poultry in sub-Saharan Africa. In some countries, repeated outbreaks have a major impact on local economies and food security. Recently, we developed an adenovirus-vectored vaccine encoding the Fusion protein from an Ethiopian isolate of Newcastle disease virus (NDV). The adenoviral vector was designed, and a manufacturing process was developed in the context of the Livestock Vaccine Innovation Fund initiative funded by the International Development Research Centre (IDRC) of Canada. The industrially relevant recombinant vaccine technology platform is being transferred to the National Veterinary Institute (Ethiopia) for veterinary applications. Here, a manufacturing process using HEK293SF suspension cells cultured in stirred-tank bioreactors for the vaccine production is proposed. Taking into consideration supply chain limitations, options for serum-free media selection were evaluated. A streamlined downstream process including a filtration, an ultrafiltration, and a concentration step was developed. With high volumetric yields (infectious titers up to 5 × 109 TCID50/mL) in the culture supernatant, the final formulations were prepared at 1010 TCID50/mL, either in liquid or lyophilized forms. The liquid formulation was suitable and safe for mucosal vaccination and was stable for 1 week at 37 °C. Both the liquid and lyophilized formulations were stable after 6 months of storage at 4 °C. We demonstrate that the instillation of the adenoviral vector through the nasal cavity can confer protection to chickens against a lethal challenge with NDV. Overall, a manufacturing process for the adenovirus-vectored vaccine was developed, and protective doses were determined using a convenient route of delivery. Formulation and storage conditions were established, and quality control protocols were implemented.

9.
Front Microbiol ; 13: 1054651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406388

RESUMO

Adenovirus vector vaccines have been the mainstream research direction of CSF vaccines, due to the replication deficiency of adenovirus vectors, achieving double effects with the safety of inactivated vaccines and the efficacy of live vaccines. Therefore, the E0 and E2 genes were expressed by an adenovirus vector, a recombinant adenovirus E0-E2 (rAd-E0-E2) vaccine was constructed, and the minimum immunization dose and immune duration period were determined in this study. Forty healthy piglets were randomly divided into 8 groups (n = 5). Groups 1 ~ 5 were used to determine the minimum immunization dose, and 5 groups were inoculated with rAd-E0-E2 at different immune doses. Serum was collected at 7 d and 14 d after immunization to detect CSFV antibodies by ELISA, and piglets were challenged at 7 d post immunization. Groups 6 ~ 8 were immunized with 1 dose of rAd-E0-E2, the CSFV live attenuated vaccine C strain and saline to identify the immune duration period. Serum was collected at different time points after immunization, CSFV antibodies were detected by ELISA, and piglets were challenged at 8 months post immunization. Meanwhile, temperature, clinical symptoms and pathology were observed. The results of groups 1 ~ 5 showed that 1 piglet was protected after challenge, and 4 piglets exhibited high fever retention, typical CSFV symptoms and tissue lesions in the 1/50 dose group, whereas no clinical symptoms were observed in the 1/10 dose, 1/5 dose or 1 dose groups with 5/5 protection after challenge. The minimum dose was determined as 1/10 dose. The results of groups 6 ~ 8 showed that all piglets survived after challenge, but the antibody level of the rAd-E0-E2 strain was higher than that of the C strain at 8 months post immunization, and all piglets in the negative group developed the disease process after challenge. Overall, the minimum immunization dose of rAd-E0-E2 was 1/10 dose (3.16 × 106.0 IFU) and the minimum immune dose was determined to be 1 dose (3.16 × 107.0 IFU) to achieve the expected effects. The immune duration period of piglets immunized with 1 dose of rAd-E0-E2 was at least 8 months.

10.
Int J Infect Dis ; 124: 206-211, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36155824

RESUMO

OBJECTIVES: To compare messenger RNA (mRNA)-based and adenovirus-vectored vaccines (ADVVs) with inactivated virus vaccines (IVVs) using real-world aggregate data. METHODS: We performed longitudinal analyses of publicly accessible epidemiological, clinical, virological, vaccine-related, and other public health data from 41 eligible countries during the first half of 2021. The relationships between vaccination coverage and clinical outcomes were analyzed using repeated measures correlation analyses and mixed-effects modeling to adjust for potential mediating and confounding factors. RESULTS: Countries that used mRNA and/or ADVV (n = 31) vs IVV, among other vaccine types (n = 10), had different distributions of age (42.4 vs 33.9 years, respectively; P-value = 0.0006), gross domestic product per capita ($ 38,606 vs $ 20,422, respectively; P <0.0001), and population sizes (8,655,541 vs 5,139,162, respectively; P-value = 0.36). After adjustment for country differences, the stringency of nonpharmaceutical interventions, and dominant SARS-CoV-2 variant types, populations that received mRNA and/or ADVV had significantly lower rates of cases and deaths over time (P <0.001 for each analysis). Populations vaccinated with IVV, among others, had significantly higher rates of cases and deaths over time (P <0.05 for each analysis). CONCLUSION: The real-world effectiveness of IVV may be inferior to mRNA and/or ADVV, and prospective comparative studies are needed to critically evaluate the role of IVV in the context of contemporary SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Adulto , SARS-CoV-2/genética , Vacinas contra COVID-19 , Estudos Prospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas de Produtos Inativados , RNA Mensageiro , Vacinação
11.
Viruses ; 14(8)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-36016401

RESUMO

Chikungunya virus (CHIKV) is a mosquito-borne virus. The emergence of CHIKV infection has raised global concern, and there is a growing need to develop safe and effective vaccines. Here, adenovirus 5 was used as the vaccine vector to construct recombinant adenoviruses expressing CHIKV E2, E1, and E2-6K-E1, respectively. And then the immunogenicity and protective efficiency against CHIKV were evaluated in BALB/c mice. Compared to the ad-wt control group, all three vaccines elicited significant humoral and cellar immune responses. The levels of neutralizing antibodies in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups both reached 1:256, which were 3.2 times higher than those in the rAd-CHIKV-E1 group. Furthermore, the levels of lymphocyte proliferation in rAd-CHIKV-E2-6K-E1 group were the highest. Besides, the concentrations of IFN-γ and IL-4 in mice immunized with rAd-CHIKV-E2-6K-E1 were 1.37 and 1.20 times higher than those in ad-wt immunized mice, respectively. After the challenge, mice in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups lost 2% of their body weight compared with 5% in the ad-wt control group. And low viral loads were detected in the heart, kidney, and blood of mice immunized with rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 at 3-5 dpc, which decreased by 0.4-0.7 orders of magnitude compared with the ad-wt control. Overall, these data suggest that the recombinant adenovirus is a potential candidate vaccine against CHIKV.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Febre de Chikungunya , Vírus Chikungunya , Vacinas Virais , Adenoviridae/genética , Animais , Anticorpos Antivirais , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/genética , Camundongos , Mosquitos Vetores , Vacinas Sintéticas/genética , Proteínas do Envelope Viral , Vacinas Virais/genética
12.
Life (Basel) ; 12(8)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35892907

RESUMO

Cerebral venous thrombosis (CVT) is a rare type of stroke that may cause an intracranial hypertension syndrome as well as focal neurological deficits due to venous infarcts. MRI with venography is the method of choice for diagnosis, and treatment with anticoagulants should be promptly started. CVT incidence has increased in COVID-19-infected patients due to a hypercoagulability state and endothelial inflammation. CVT following COVID-19 vaccination could be related to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare but severe complication that should be promptly identified because of its high mortality rate. Platelet count, D-dimer and PF4 antibodies should be dosed. Treatment with non-heparin anticoagulants and immunoglobulin could improve recuperation. Development of headache associated with seizures, impaired consciousness or focal signs should raise immediate suspicion of CVT. In patients who received a COVID-19 adenovirus-vector vaccine presenting thromboembolic events, VITT should be suspected and rapidly treated. Nevertheless, vaccination benefits clearly outweigh risks and should be continued.

13.
Cell Rep Med ; 3(7): 100679, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35798000

RESUMO

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.


Assuntos
COVID-19 , Vacinas Virais , Ad26COVS1 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , RNA Mensageiro , SARS-CoV-2/genética , Vacinas Sintéticas , Vacinas de mRNA
14.
Vaccines (Basel) ; 10(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35335098

RESUMO

Vaccine hesitancy due to safety concerns is a hindrance to the success of vaccination campaigns. In February 2021, Trinidad and Tobago commenced its National COVID-19 Vaccination Program. Healthcare workers were among the first group to receive the ChAdOx1 nCoV-19 (Oxford−AstraZeneca (Covishield, Serum Institute of India, Pune, India), the first COVID-19 vaccine available nationally. This study examined the safety of this vaccine in terms of the systemic and local adverse events following immunization reported by healthcare worker recipients. A cross-sectional study was conducted via a telephone questionnaire. Data concerning demographics, medical and COVID-19-related anamneses, and local and systemic side effects experienced within the first 48 h after receiving the first and second dose of this vaccine, respectively, were gathered. Among the 687 participants (male = 275; female = 412), prevalence of fever, body pain, chills, nausea, myalgia, headache, malaise, fatigue, and other systemic symptoms declined significantly 48 h after administration of the second dose compared to the first dose. Chi-square test and multiple logistic regression demonstrated the greater likelihood of younger recipients to report systemic symptoms compared to older recipients. Multiple logistic regression indicated that females were more likely to report headache, fatigue, and discomfort, and were less likely to report no symptoms, compared to males, after both doses. On average, recipients reported less local and systemic side effects 48 h after receiving the second dose compared to the first dose. The reported rate of occurrence of side effects was <50% for most adverse events, which is consistent with the manufacturer's claims that the vaccine is safe. This study adds data on the safety of this vaccine in a population that has not been previously studied. The findings can inform public health policy efforts to lower vaccine hesitancy based on safety concerns surrounding the ChAdOx1 nCoV-19 vaccine across various groups in society, including healthcare workers.

15.
Infect Agent Cancer ; 17(1): 5, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35197089

RESUMO

OBJECTIVE: This study aims to prepare candidate vaccines for cervical cancer immunotherapy by inserting the fused genes of human papillomavirus (HPV)16/18/58 mE6E7 lacking transforming activity into an adenovirus vector and to verify its efficiency in model mice with tumor expressing the associated HPV genes. METHODS: The E6/E7 genes of HPV16/18/58 were point-mutated to abolish their transforming activity, and adenovirus (AD)-HPV16/18/58 mE6E7 adenovirus vaccine was constructed. The immune effect of the adenovirus vaccine against HPV16/18/58-type tumors was analyzed by tumor morphology, enzyme linked immunosorbent assay, enzyme-linked immunospot and specific cytotoxic T lymphocyte (CTL) and T lymphocyte subsets. RESULTS: The HPV16/18/58 mE6E7 plasmid containing point mutations was verified by quantitative real-time polymerase chain reaction (qRT-PCR), enzyme digestion and electrophoresis, and gene sequencing. qRT-PCR and Western blots verified that AD-HPV16/18/58 mE6E7 could express the HPV16 mE6E7, HPV18 mE6E7 and HPV58 mE6E7 fusion genes and proteins in cells. The results of animal experiments were as follows: In the vaccine group, the tumors formed later, the incubation period was longer, the growth was slower, growth was inhibited, and the survival period was significantly prolonged. The immunological results all showed that the vaccine could induce effective humoral and cellular immunity in mice with three types of tumors, compared with the phosphate buffered saline (PBS) group and the adenovirus-negative control (AD-NC) group, the differences were statistically significant (P < 0.05). CONCLUSION: We successfully constructed the HPV16/18/58 trivalent therapeutic adenovirus vaccine AD-HPV16/18/58 mE6E7. The AD-HPV16/18/58 mE6E7 adenovirus vaccine can protect immunized mice to a certain extent from TC-1, U14/LV-HPV18 E6E7 and U14/LV-HPV58 E6E7 cells, which contain HPV16, 18 and 58 E6 and/or E7 genes, respectively.

16.
Pharmacol Res ; 175: 106034, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34915126

RESUMO

Renal carcinoma progresses aggressively in patients with metastatic disease while curative strategies are limited. Here, we constructed a recombinant non-replicating adenovirus (Ad) vaccine encoding an immune activator, CD137L, and a tumor antigen, CAIX, for treating renal carcinoma. In a subcutaneous tumor model, tumor growth was significantly suppressed in the Ad-CD137L/CAIX vaccine group compared with the single vaccine group. The induction and maturity of CD11C+ and CD8+CD11C+ dendritic cell (DC) subsets were promoted in Ad-CD137L/CAIX co-immunized mice. Furthermore, the Ad-CD137L/CAIX vaccine elicited stronger tumor-specific multifunctional CD8+ T cell immune responses as demonstrated by increased proliferation and cytolytic function of CD8+ T cells. Notably, depletion of CD8+ T cells greatly compromised the effective protection provided by Ad-CD137L/CAIX vaccine, suggesting an irreplaceable role of CD8+ T cells for the immunopotency of the vaccine. In both lung metastatic and orthotopic models, Ad-CD137L/CAIX vaccine treatment significantly decreased tumor metastasis and progression and increased the induction of tumor-specific multifunctional CD8+ T cells, in contrast to treatment with the Ad-CAIX vaccine alone. The Ad-CD137L/CAIX vaccine also augmented the tumor-specific multifunctional CD8+ T cell immune response in both orthotopic and metastatic models. These results indicated that Ad-CD137L/CAIX vaccine elicited a potent anti-tumor activity by inducing CD8+DC-mediated multifunctional CD8+ T cell immune responses. The potential strategy of CD137L-based vaccine might be served as a novel treatment for renal carcinoma or other malignant tumors.


Assuntos
Ligante 4-1BB/genética , Vacinas contra Adenovirus/uso terapêutico , Anidrase Carbônica IX/genética , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Neoplasias Pulmonares/terapia , Ligante 4-1BB/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Anidrase Carbônica IX/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Células Dendríticas/imunologia , Feminino , Células HEK293 , Humanos , Interleucina-6/sangue , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos BALB C
17.
Chinese Critical Care Medicine ; (12): 571-575, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-956012

RESUMO

Objective:To analyze the clinical characteristics of patients inoculated with different vaccines and underlying diseases, infected with the novel coronavirus Omicron variant.Methods:The data of 430 patients infected with the novel coronavirus Omicron variant who were admitted to Tianjin First Center Hospital from January 21, 2022 to March 7, 2022 were collected. A total of 108 patients with Omicron variant infection with underlying diseases were selected and enrolled. The gender, age, body mass index (BMI), history of underlying diseases, vaccination status (vaccination times, vaccination type), clinical symptoms, laboratory test indicators, imaging data, hospitalization time, nucleic acid negative conversion time, re-positivity and antibody titer from the two groups of the patients were collected and analyzed.Results:In the 108 patients, 93 cases received inactivated vaccine and 15 cases received adenovirus vaccine. There was no statistically significant difference between the two groups in terms of gender, age, BMI, disease types, whether completed the fully vaccinated, whether had prime boost and underlying diseases. Both groups had fever, dry cough, sore throat, runny nose and other clinical symptoms, but there were no statistical difference between the two groups. There were no statistically significant differences in laboratory blood routine tests, biochemical indexes, C-reactive protein (CRP) level and the results of chest computed tomography (CT) imaging between the two groups. There were no statistically significant differences in hospitalization days, nucleic acid negative conversion time, whether admission to intensive care unit (ICU), turn re-positive on nucleic acid tests and immunoglobulin M (IgM) antibody titer expression between the two groups, but immunoglobulin G (IgG) antibody titer in adenovirus group was higher than that in inactivated group (g/L: 229.67±26.13 vs. 194.33±61.56, P = 0.020). There were also no significant differences in laboratory examinations, hospitalization days, nucleic acid negative conversion time, turn re-positive on nucleic acid tests and Novel coronavirus antibody titers expression of the patients with booster shots between the inactivated vaccine group and the adenovirus vaccine group. Conclusions:The protection of inactivated virus vaccine is equivalent to adenovirus vaccine in patients with underlying disease Omicron variant infection, and the titer of IgG antibody in patients with adenovirus vaccine is higher than that in patients with inactivated virus vaccine after one week of recovery.

18.
Vaccines (Basel) ; 9(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34960232

RESUMO

We present a case of immune thrombocytopenia (ITP) induced by the chimpanzee adenovirus-vectored vaccine, without evidence of thrombosis, eight days after vaccine administration. The thrombocytopenia condition improved after administering steroid treatment. This adenovirus vaccine had been reported to induce rare side effects, such as immune thrombotic thrombocytopenia. This case report showed that it could also induce immune thrombocytopenia without the presence of thrombosis. Therefore, we should be cautious of this rare side effect as global vaccine administrations against coronavirus disease increase.

19.
Cureus ; 13(9): e18153, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34703690

RESUMO

Efforts to combat the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) range from adequate diagnostic testing and contract tracing to vaccination for the prevention of coronavirus disease 2019 (COVID-19). In the United States alone, three vaccinations have been authorized for emergency use (EUA) or approved to prevent COVID-19. The Ad26.COV2.S vaccine by Johnson and Johnson (New Brunswick, New Jersey) is the only adenovirus-based vaccine and deemed relatively effective and safe by the US Food and Drug Administration (FDA) following its clinical trial. Since its introduction, the US FDA has placed a warning on the vaccine adverse event reporting system (VAERS) after more than 100 cases of Guillain-Barre Syndrome (GBS) were reported. Herein, we outline the hospital course of a generally healthy 49-year-old female who experienced an axonal form of GBS nine days after receiving the Ad26.COV2.S vaccine.

20.
Pharmaceuticals (Basel) ; 14(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358101

RESUMO

Foot and mouth disease is a highly contagious disease affecting cattle, sheep, and swine among other cloven-hoofed animals that imposes serious economic burden by its direct effects on farm productivity as well as on commerce of farmed produce. Vaccination using inactivated viral strains of the different serotypes is an effective protective measure, but has several drawbacks including a lack of cross protection and the perils associated with the large-scale growth of infectious virus. We have previously developed chimeric virus-like particles (VLPs) bearing an FMDV epitope which induced strong specific humoral responses in vaccinated pigs but conferred only partial protection against homologous challenge. While this and other FMD vaccines under development mostly rely on the induction of neutralizing responses, it is thought that induction of specific T-cell responses might improve both cross protective efficacy as well as duration of immunity. Therefore, we here describe the development of a recombinant adenovirus expressing the highly conserved nonstructural FMDV 3D protein as well as its capacity to induce specific T-cell responses in a murine model. We further describe the generation of an FMDV serotype C-specific chimeric VLP and analyze the immunogenicity of two different prime-boost strategies combining both elements in mice. This combination can effectively induce both humoral and cellular FMDV-specific responses eliciting high titers of ELISA and neutralizing antibodies anti-FMDV as well as a high frequency of IFNγ-secreting cells. These results provide the basis for further testing of this anti FMD vaccination strategy in cattle or pig, two of the most relevant natural host of this pathogen.

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