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1.
Front Immunol ; 13: 837443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281065

RESUMO

An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (eVLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made eVLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated eVLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered eVLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Proteínas M de Coronavírus/imunologia , Giardia lamblia/imunologia , Mucosa Intestinal/imunologia , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Antígenos de Protozoários/imunologia , Cricetinae , Humanos , Imunidade , Imunização Secundária , Imunoglobulina A/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Temperatura , Potência de Vacina , Vacinas de Partículas Semelhantes a Vírus
3.
Biologicals ; 76: 10-14, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35264299

RESUMO

Several glycoconjugate vaccines have been licensed or are currently in clinical development to prevent bacterial infections. Here we report the development of a single analytical assay to quantify the conjugated saccharide content, as alternative to two separated total and free (unconjugated) saccharide assays used so far, for a quadrivalent conjugate vaccine containing meningococcal serogroup A polysaccharide (α-1,6-linked N-acetylmannosamine phosphate repeating unit partly O-acetylated at position C3 or C4) coupled with CRM197 protein. The results confirm a high linear correlation among the two approaches (conjugated saccharide content vs. difference of total saccharide and free saccharide). Conjugated saccharide content estimation is therefore demonstrated to be a suitable method to monitor the product quality of vaccines containing meningococcal serogroup A conjugate antigen, in the final filled presentation as demonstrated here and potentially on the bulk conjugate before formulation.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Anticorpos Antibacterianos , Glicoconjugados , Humanos , Infecções Meningocócicas/prevenção & controle , Potência de Vacina , Vacinas Conjugadas
4.
Cell Rep ; 38(9): 110429, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35216664

RESUMO

Continuous emergence of SARS-CoV-2 variants of concern (VOCs) is fueling the COVID-19 pandemic. Omicron (B.1.1.529) rapidly spread worldwide. The large number of mutations in its Spike raise concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses elicits antibodies that efficiently recognize Spikes from different VOCs. Here, we evaluate the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously infected individuals who received their BNT162b2 mRNA vaccine 16 weeks apart. Omicron Spike is recognized less efficiently than D614G, Alpha, Beta, Gamma, and Delta Spikes. We compare with plasma activity from participants receiving a short (4 weeks) interval regimen. Plasma from individuals of the long-interval cohort recognize and neutralize better the Omicron Spike compared with those who received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.


Assuntos
Anticorpos Neutralizantes/sangue , Esquemas de Imunização , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Estudos de Coortes , Feminino , Células HEK293 , Humanos , Imunização Secundária/métodos , Masculino , Pessoa de Meia-Idade , Quebeque , SARS-CoV-2/patogenicidade , Fatores de Tempo , Vacinação/métodos , Potência de Vacina , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Adulto Jovem , /imunologia
5.
Viral Immunol ; 35(2): 159-169, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35104162

RESUMO

Rabies vaccine preparations are quantitatively assayed for potency using the in-vivo challenge National Institute of Health (NIH), the main test that consumes a high number of animals, takes a long time, and has wide variability. The Rapid focus fluorescent inhibition (RFFIT) and the passive hemagglutination (PHA) tests, the two serologically based tests, were also used for such purpose. In this study, we aimed to evaluate and correlate the potency of the NIH, RFFIT, and PHA tests according to the World Health Organization (WHO) validity criteria, aiming to validate the use of RFFIT or PHA test as a substitute to the NIH test for determining the potency of commercially available Rabies vaccine preparations. The results showed that, the three tests can be successfully used; however, a higher correlation between RFFIT and NIH than PHA and NIH was recorded (Pearson correlation = 1). The potency of rabies vaccine preparations using NIH, RFFIT, and PHA were 3.73, 3.51, and 4.50, respectively. NIH is the main test for the determination of vaccine potency carried out by conducting 25 experiments and consuming about 5,000 mice compared to 1,200 mice used with RFFIT and 1,000 mice used with PHA test. Taken together, we concluded that (i) in some tested preparations, both RFFIT and PHA tests gave comparable results, and they can be used interchangeably; (ii) RFFIT could successfully replace NIH test, but not PHA; (iii) RFFIT and PHA tests are faster, more accurate, more economic, and more sensitive than NIH; nevertheless, PHA needs further investigations; and (iv) both RFFIT and NIH tests complement and reinforce each other as they provide a comprehensive picture of the product potency.


Assuntos
Vacinas Antirrábicas , Vírus da Raiva , Raiva , Animais , Anticorpos Antivirais , Testes de Hemaglutinação , Camundongos , Testes de Neutralização/métodos , Raiva/prevenção & controle , Potência de Vacina
6.
Viruses ; 14(1)2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-35062300

RESUMO

The recent emergence and circulation of the A/ASIA/G-VII (A/G-VII) lineage of foot-and-mouth disease virus (FMDV) in the Middle East has resulted in the development of homologous vaccines to ensure susceptible animals are sufficiently protected against clinical disease. However, a second serotype A lineage called A/ASIA/Iran-05 (A/IRN/05) continues to circulate in the region and it is therefore imperative to ensure vaccine strains used will protect against both lineages. In addition, for FMDV vaccine banks that usually hold a limited number of strains, it is necessary to include strains with a broad antigenic coverage. To assess the cross protective ability of an A/G-VII emergency vaccine (formulated at 43 (95% CI 8-230) PD50/dose as determined during homologous challenge), we performed a heterologous potency test according to the European Pharmacopoeia design using a field isolate from the A/IRN/05 lineage as the challenge virus. The estimated heterologous potency in this study was 2.0 (95% CI 0.4-6.0) PD50/dose, which is below the minimum potency recommended by the World Organisation for Animal Health (OIE). Furthermore, the cross-reactive antibody titres against the heterologous challenge virus were poor (≤log10 0.9), even in those cattle that had received the full dose of vaccine. The geometric mean r1-value was 0.2 (95% CI 0.03-0.8), similar to the potency ratio of 0.04 (95% CI 0.004-0.3). Vaccination decreased viraemia and virus excretion compared to the unvaccinated controls. Our results indicate that this A/G-VII vaccine does not provide sufficient protection against viruses belonging to the A/IRN/05 lineage and therefore the A/G-VII vaccine strain cannot replace the A/IRN/05 vaccine strain but could be considered an additional strain for use in vaccines and antigen banks.


Assuntos
Doenças dos Bovinos/prevenção & controle , Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Imunidade Heteróloga , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/virologia , Proteção Cruzada , Febre Aftosa/imunologia , Febre Aftosa/virologia , Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/isolamento & purificação , RNA Viral/análise , Sorogrupo , Potência de Vacina , Viremia/prevenção & controle , Viremia/veterinária , Eliminação de Partículas Virais
7.
Cell Rep ; 38(5): 110318, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35090597

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Nanopartículas/administração & dosagem , SARS-CoV-2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Vacinas contra COVID-19/química , Vacinas contra COVID-19/genética , Cricetinae , Epitopos , Cobaias , Imunogenicidade da Vacina , Camundongos , Nanopartículas/química , /química , /imunologia , Polissacarídeos/química , Polissacarídeos/genética , Polissacarídeos/imunologia , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Potência de Vacina
8.
Emerg Microbes Infect ; 11(1): 384-391, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35001848

RESUMO

This paper presents the key outcomes of the above WHO informal consultation with global stakeholders including regulatory authorities, vaccine developers and manufacturers, academia and other international health organizations and institutions involved in the development, evaluation and use of messenger RNA (mRNA) vaccines. The aim of the consultation was to further clarify the main principles to be presented in an upcoming WHO guidance document on the regulatory considerations in evaluating the quality, safety and efficacy of mRNA prophylactic vaccines for infectious diseases. This WHO guidance document is intended to facilitate global mRNA vaccine development and regulatory convergence in the assessment of such vaccines. The urgent need to develop such a document as a new WHO written standard is outlined in this report along with the key scientific and regulatory challenges. A number of key conclusions are provided at the end of this report along with an update on the steps taken following this meeting.


Assuntos
Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/uso terapêutico , /uso terapêutico , COVID-19/prevenção & controle , Humanos , Potência de Vacina , Organização Mundial da Saúde
10.
Fish Shellfish Immunol ; 120: 133-138, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34780977

RESUMO

Pseudomonas plecoglossicida is the causative agent of visceral granulomas disease (VGD) in large yellow croaker (LYC, Larimichthys crocea) farming. However, multi-antibiotic resistant of P. plecoglossicida creates an urgent need of an efficient vaccine to combat this pathogen. In this study, an inactivated vaccine added polyactin (PA), CpG-riched plasmid (pCpG) and aluminum adjuvant (Al) was developed. As a result, its relative percentage survival (RPS) against P. plecoglossicida were up to 64%. Comparatively, RPS of groups that vaccinated with vaccines adjuvanted with PA and Al or CpG and Al were 49% and 39%. However, an interesting result that the vaccine combined with PA, CpG and Al did not show the strongest activation of total serum protein and antibody levels in serum among three vaccinated groups. According to expressions of some cellular immune related genes, we found that the inactivated vaccine combined with PA, CpG and Al was more likely to induce a cellular immune response rather than humoral immune response. Totally, our study demonstrated that the mixture of PA, CpG and aluminum adjuvant is a potential adjuvant system for LYC vaccine development.


Assuntos
Vacinas Bacterianas/imunologia , Ilhas de CpG , Doenças dos Peixes , Glicopeptídeos/farmacologia , Perciformes , Infecções por Pseudomonas , Potência de Vacina , Adjuvantes Imunológicos , Alumínio , Animais , Doenças dos Peixes/prevenção & controle , Perciformes/imunologia , Perciformes/microbiologia , Pseudomonas , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/veterinária , Vacinas de Produtos Inativados
11.
Science ; 375(6577): 183-192, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-34855510

RESUMO

The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.


Assuntos
/imunologia , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Vacinas contra COVID-19/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteção Cruzada , Feminino , Pessoal de Saúde , Humanos , Estudos Longitudinais , Masculino , Mutação , Fosfoproteínas/imunologia , Domínios Proteicos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Vacinação , Potência de Vacina
12.
Methods Mol Biol ; 2410: 693-705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34914076

RESUMO

The issues of vaccine potency and stability constitute formidable challenges associated with the development and readiness of vaccines for biodefense. In most instances, the vaccines will be stockpiled (at considerable cost) for years and used only in the rare event of a public health emergency. It is therefore imperative that there be means to readily monitor overall stability of the stockpiled vaccines, preferably using reliable in vitro assays, without the need for expensive and labor-intensive animal studies. In this chapter, we describe an in vitro monoclonal antibody-based competition ELISA known as RiCoE for assessing the potency of a ricin toxin subunit vaccine. RiCoE can be applied to drug substance and drug products adsorbed to aluminum salts adjuvant. While RiCoE is specific for ricin toxin, the general methodologies and protocols described herein are amenable to virtually any subunit or even virus-like particle-based vaccine. Ultimately, RiCoE-like assays may replace or at least reduce the need for animal studies in vaccine potency determinations.


Assuntos
Potência de Vacina , Adjuvantes Farmacêuticos , Animais , Anticorpos Neutralizantes , Ricina , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus
13.
J Control Release ; 342: 388-399, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34896446

RESUMO

The efficacy of RNA-based vaccines has been recently demonstrated, leading to the use of mRNA-based COVID-19 vaccines. The application of self-amplifying mRNA within these formulations may offer further enhancement to these vaccines, as self-amplifying mRNA replicons enable longer expression kinetics and more potent immune responses compared to non-amplifying mRNAs. To investigate the impact of administration route on RNA-vaccine potency, we investigated the immunogenicity of a self-amplifying mRNA encoding the rabies virus glycoprotein encapsulated in different nanoparticle platforms (solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNPs) and lipid nanoparticles (LNPs)). These were administered via three different routes: intramuscular, intradermal and intranasal. Our studies in a mouse model show that the immunogenicity of our 4 different saRNA vaccine formulations after intramuscular or intradermal administration was initially comparable; however, ionizable LNPs gave higher long-term IgG responses. The clearance of all 4 of the nanoparticle formulations from the intramuscular or intradermal administration site was similar. In contrast, immune responses generated after intranasal was low and coupled with rapid clearance for the administration site, irrespective of the formulation. These results demonstrate that both the administration route and delivery system format dictate self-amplifying RNA vaccine efficacy.


Assuntos
COVID-19 , Nanopartículas , Animais , Vacinas contra COVID-19 , Humanos , Lipossomos , Camundongos , RNA Mensageiro , SARS-CoV-2 , Potência de Vacina , Vacinas Sintéticas
14.
J Autoimmun ; 125: 102744, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34781162

RESUMO

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53-1203) vs 825 (451-1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals.


Assuntos
/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , /imunologia , COVID-19/prevenção & controle , Feminino , Humanos , Itália , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/imunologia , Escleroderma Sistêmico/imunologia , Vasculite Sistêmica/imunologia , Vacinação , Potência de Vacina
15.
Nat Commun ; 12(1): 6777, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811367

RESUMO

Lipid nanoparticle (LNP)-formulated mRNA vaccines were rapidly developed and deployed in response to the SARS-CoV-2 pandemic. Due to the labile nature of mRNA, identifying impurities that could affect product stability and efficacy is crucial to the long-term use of nucleic-acid based medicines. Herein, reversed-phase ion pair high performance liquid chromatography (RP-IP HPLC) was used to identify a class of impurity formed through lipid:mRNA reactions; such reactions are typically undetectable by traditional mRNA purity analytical techniques. The identified modifications render the mRNA untranslatable, leading to loss of protein expression. Specifically, electrophilic impurities derived from the ionizable cationic lipid component are shown to be responsible. Mechanisms implicated in the formation of reactive species include oxidation and subsequent hydrolysis of the tertiary amine. It thus remains critical to ensure robust analytical methods and stringent manufacturing control to ensure mRNA stability and high activity in LNP delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos , Lipossomos/química , Nanopartículas/química , RNA Mensageiro/química , Potência de Vacina , Aldeídos/química , Cromatografia Líquida , Humanos , Íons/química , Lipídeos/química , Nucleosídeos/química , Oxirredução , Biossíntese de Proteínas , Estabilidade de RNA , /química
16.
JAMA Netw Open ; 4(10): e2130800, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34714342

RESUMO

Importance: Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking. Objective: To assess whether the pragmatic application of the 3 COVID-19 vaccines available in Argentina, 2 of which have no reports of evaluation in real-world settings to date, were associated with a reduction in morbidity, all-cause mortality, and mortality due to COVID-19. Design, Setting, and Participants: This cohort study used individual and ecological data to explore outcomes following vaccination with rAd26-rAd5, ChAdOx1, and BBIBP-CorV. To correct for differences in exposure times, results are shown using incidence density per 100 000 person-days from the start of the vaccination campaign (December 29, 2020) to the occurrence of an event or the end of follow-up (May 15, 2021). Participants included 663 602 people aged at least 60 years residing in the city of Buenos Aires, Argentina. Statistical analysis was performed from June 1 to June 15, 2021. Main Outcomes and Measures: Diagnosis of COVID-19 confirmed by reverse transcription-polymerase chain reaction, death from all causes, and death within 30 days of a diagnosis of COVID-19. Poisson regression models were fitted to estimate associations with all 3 outcomes. Results: Among 663 602 residents of the city of Buenos Aires included in the study, 540 792 (81.4%) were vaccinated with at least 1 dose, with 457 066 receiving 1 dose (mean [SD] age, 74.5 (8.9) years; 61.5% were female [n = 281 284]; 68.0% [n = 310 987] received the rAd26-rAd5 vaccine; 29.5% [n = 135 036] received ChAdOx1; 2.4% [n = 11 043] received BBIBP-CorV) and 83 726 receiving 2 doses (mean [SD] age, 73.4 [6.8] years; 63.5% were female [n = 53 204]). The incidence density of confirmed COVID-19 was 36.25 cases/100 000 person-days (95% CI, 35.80-36.70 cases/100 000 person-days) among those who did not receive a vaccine, 19.13 cases/100 000 person-days (95% CI, 18.63-19.62 cases/100 000 person-days) among those who received 1 dose, and 4.33 cases/100 000 person-days (95% CI, 3.85-4.81 cases/100 000 person-days) among those who received 2 doses. All-cause mortality was 11.74 cases/100 000 person-days (95% CI, 11.51-11.96 cases/100 000 person-days), 4.01 cases/100 000 person-days (95% CI, 3.78-4.24 cases/100 000 person-days) and 0.40 cases/100 000 person-days (95% CI, 0.26-0.55 cases/100 000 person-days). COVID-19-related-death rate was 2.31 cases/100 000 person-days (95% CI, 2.19-2.42 cases/100 000 person-days), 0.59 cases/100 000 person-days (95% CI, 0.50-0.67 cases/100 000 person-days), and 0.04 cases/100 000 person-days (95% CI, 0.0-0.09 cases/100 000 person-days) among the same groups. A 2-dose vaccination schedule was associated with an 88.1% (95% CI, 86.8%-89.2%) reduction in documented infection, 96.6% (95% CI, 95.3%-97.5%) reduction in all-cause death, and 98.3% (95% CI, 95.3%-99.4%) reduction in COVID-19-related death. A single dose was associated with a 47.2% (95% CI, 44.2%-50.1%) reduction in documented infection, 65.8% (95% CI, 61.7%-69.5%) reduction in all-cause death, and 74.5% (95% CI, 66%-80.8%) reduction in COVID-19-related death. Conclusions and Relevance: This study found that within the first 5 months after the start of the vaccination campaign, vaccination was associated with a significant reduction in COVID-19 infection as well as a reduction in mortality.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Programas de Imunização , Cobertura Vacinal/estatística & dados numéricos , Idoso , Argentina/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/prevenção & controle , Teste de Ácido Nucleico para COVID-19/métodos , Vacinas contra COVID-19/classificação , Vacinas contra COVID-19/uso terapêutico , Estudos de Coortes , Monitorização de Parâmetros Ecológicos/métodos , Monitorização de Parâmetros Ecológicos/estatística & dados numéricos , Feminino , Humanos , Programas de Imunização/métodos , Programas de Imunização/organização & administração , Programas de Imunização/estatística & dados numéricos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , SARS-CoV-2/imunologia , Potência de Vacina
17.
Sci Rep ; 11(1): 20877, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686689

RESUMO

Adenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2-8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.


Assuntos
Adenoviridae/genética , Vacinas contra Adenovirus/química , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Potência de Vacina , Adenovirus dos Símios , Materiais Biocompatíveis , Varredura Diferencial de Calorimetria , Vidro , Células HEK293 , Humanos , Luz , Espectroscopia de Ressonância Magnética , Teste de Materiais , Microscopia Confocal , Microscopia Eletrônica de Varredura , Álcool de Polivinil , Vacinas Antirrábicas , Espalhamento de Radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Açúcares/química , Temperatura , Termogravimetria , Trealose/química
18.
Science ; 373(6561): eabj0299, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34529476

RESUMO

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 µg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti­S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273­induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine­induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/virologia , Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , COVID-19/virologia , Feminino , Esquemas de Imunização , Imunização Passiva , Imunização Secundária , Imunoglobulina G/imunologia , Memória Imunológica , Pulmão/imunologia , Pulmão/virologia , Macaca mulatta , Masculino , Mesocricetus , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Potência de Vacina , Replicação Viral
20.
J Vet Med Sci ; 83(11): 1694-1701, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34526415

RESUMO

Sporadic spreads of swine-origin influenza H3N2 variant (H3N2v) viruses were reported in humans, resulting in 437 human infections between 2011 and 2021 in the USA. Thus, an effective vaccine is needed to better control a potential pandemic for these antigenically distinct viruses from seasonal influenza. In this study, a candidate vaccine strain with efficient growth capacity in chicken embryos was established through serial blind passaging of A/Indiana/08/2011 (H3N2)v in mice and chicken embryos. Seven amino acid substitutions (M21I in PA; A138T, N165K, and V226A in HA; S312L in NP; T167I in M1; G62A in NS1 proteins) were found in the passaged viruses without a major change in the antigenicity. This mouse- and egg-adapted virus was used as a vaccine and challenge strain in mice to evaluate the efficacy of the H3N2v vaccine in different doses. Antibodies with high neutralizing titers were induced in mice immunized with 100 µg of inactivated whole-virus particles, and those mice were significantly protected from the challenge of homologous strain. The findings indicated that the established strain in the study was useful for vaccine study in mouse models.


Assuntos
Vacinas contra Influenza , Influenza Humana , Doenças dos Roedores , Substituição de Aminoácidos , Animais , Anticorpos Antivirais , Embrião de Galinha , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Camundongos , Potência de Vacina
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