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1.
Front Immunol ; 12: 740249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594343

RESUMO

Objective: To assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity. Methods: Health care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications. Results: We prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4+ and CD8+ T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination. Conclusion: This study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.


Assuntos
Anticorpos Antivirais/imunologia , Artrite Reumatoide/terapia , Vacinas contra COVID-19/imunologia , Imunoterapia/efeitos adversos , Linfócitos T/imunologia , Idoso , Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , COVID-19/prevenção & controle , Feminino , Humanos , Interferon gama/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/citologia , Vacinas Sintéticas/imunologia
2.
PLoS One ; 16(9): e0257111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543291

RESUMO

BACKGROUND: COVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage. METHODS: Our community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategy's design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients ≥16 years old were used in the evaluation. RESULTS: There were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew ≥3). Among clients who received both vaccine doses (n = 729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to ≥3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence. CONCLUSIONS: A multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.


Assuntos
Vacinas contra COVID-19/imunologia , Hispano-Americanos , Características de Residência , Adolescente , Adulto , COVID-19/imunologia , Grupos de Populações Continentais , Grupos Étnicos , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , São Francisco , Fatores de Tempo , Resultado do Tratamento , Vacinação
3.
PLoS One ; 16(9): e0257668, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543337

RESUMO

BACKGROUND: Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech's BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). METHODS AND RESULTS: Blood samples were obtained from 67 Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% confidence interval (95% CI): 855-1282 AU/mL) after the first injection to 17,378 AU/mL (95% CI: 14,622-20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, AE score after the first injection, and log-transformed spike IgG after the first injection. CONCLUSIONS: Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.


Assuntos
Grupo com Ancestrais do Continente Asiático , Vacinas contra COVID-19/imunologia , Imunoglobulina G/sangue , Injeções , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , SARS-CoV-2/fisiologia
5.
Front Immunol ; 12: 701411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539632

RESUMO

In March 2020, the World Health Organization (WHO) declared a global health emergency-the coronavirus disease 2019 (COVID-19) pandemic. Since then, the development and implementation of vaccines against the virus amidst emerging cases of re-infection has prompted researchers to work towards understanding how immunity develops and is sustained. Serological testing has been instrumental in monitoring the development and persistence of antibodies against SARS-CoV-2 infection, however inconsistencies in detection have been reported by different methods. As serological testing becomes more commonplace, it is important to establish widespread and repeatable processes for monitoring vaccine efficacy. Therefore, we present enzyme linked immunosorbent assays (ELISAs) compatible for antibody detection in saliva as highly accurate, efficacious, and scalable tools for studying the immune response in individuals vaccinated against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/análise , Anticorpos Antivirais/análise , COVID-19/imunologia , SARS-CoV-2/imunologia , Saliva/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos
6.
Front Immunol ; 12: 724060, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539660

RESUMO

Thirty-five peptides selected from functionally-relevant SARS-CoV-2 spike (S), membrane (M), and envelope (E) proteins were suitably modified for immunising MHC class II (MHCII) DNA-genotyped Aotus monkeys and matched with HLA-DRß1* molecules for use in humans. This was aimed at producing the first minimal subunit-based, chemically-synthesised, immunogenic molecules (COLSARSPROT) covering several HLA alleles. They were predicted to cover 48.25% of the world's population for 6 weeks (short-term) and 33.65% for 15 weeks (long-lasting) as they induced very high immunofluorescent antibody (IFA) and ELISA titres against S, M and E parental native peptides, SARS-CoV-2 neutralising antibodies and host cell infection. The same immunological methods that led to identifying new peptides for inclusion in the COLSARSPROT mixture were used for antigenicity studies. Peptides were analysed with serum samples from patients suffering mild or severe SARS-CoV-2 infection, thereby increasing chemically-synthesised peptides' potential coverage for the world populations up to 62.9%. These peptides' 3D structural analysis (by 1H-NMR acquired at 600 to 900 MHz) suggested structural-functional immunological association. This first multi-protein, multi-epitope, minimal subunit-based, chemically-synthesised, highly immunogenic peptide mixture highlights such chemical synthesis methodology's potential for rapidly obtaining very pure, highly reproducible, stable, cheap, easily-modifiable peptides for inducing immune protection against COVID-19, covering a substantial percentage of the human population.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Proteínas do Envelope de Coronavírus/imunologia , Proteínas M de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Subunidades/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Aotidae , COVID-19/prevenção & controle , Cadeias HLA-DRB1/genética , Humanos , Peptídeos/imunologia , SARS-CoV-2/imunologia
7.
Front Immunol ; 12: 737083, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539673

RESUMO

mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, ß, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, ß, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of ß and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Convalescença , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Estudos Longitudinais , Masculino , Espanha , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação
10.
Dtsch Med Wochenschr ; 146(19): 1277-1282, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34553353

RESUMO

HOW EFFECTIVE ARE THE APPROVED VACCINES IN KIDNEY DISEASES AND THOSE RECEIVING IMMUNOSUPPRESSION?: Several observational studies indicated that immunosuppression is associated with a weakened or absent humoral response. Patients with chronic kidney diseases or undergoing maintenance dialysis without immunosuppression have a reduced humoral response to COVID-19 vaccines. I HAD COVID-19. SHOULD I GET VACCINATED?: It is recommended to receive a booster after SARS-CoV-2 infection with a mRNA vaccine. IS A COVID-19 VACCINATION DESPITE ONGOING IMMUNOSUPPRESSION POSSIBLE?: Patients receiving immunosuppression have a reduced humoral response, and this is especially observed when anti-CD20 therapy is used. IS THERE A POSSIBILITY THAT THE VACCINE PROVOKES REJECTION OF MY TRANSPLANTED KIDNEY OR RELAPSE OF MY GLOMERULAR DISEASE?: Several reports were published in the last months highlighting new-onset diseases, recurrences and relapses of different glomerular diseases, which occurred after the receipt of the first or second vaccine dose. As a clear association of vaccines and induction of autoimmunity still needs to be established, most of these diseases are treatable, and COVID-19 in patients under immunosuppression is often fatal, there is a clear net benefit of vaccination. DO I HAVE A PERMANENT PROTECTION AFTER VACCINATION?: The antibody titers and likely the cellular immune response is significantly reduced in patients with kidney diseases, and titers are reducing at a fast pace under ongoing immunosuppression. A booster dose should be considered, especially taking into consideration the evolvement of virus variants and their impact on vaccine efficacy. AFTER THE FIRST SERIES OF VACCINATION, NO OR ONLY A MARGINAL AMOUNT OF ANTIBODIES WERE DETECTABLE. ARE THERE STRATEGIES TO IMPROVE VACCINE RESPONSE?: Many countries recommend the application of a third dose for vulnerable patient cohorts, especially because of a weakened response and their risk to develop a severe disease course of COVID-19. Prospective clinical trials are ongoing to test the ideal strategy to improve vaccine response in these cohorts.


Assuntos
Vacinas contra COVID-19 , Imunossupressores , Insuficiência Renal Crônica/terapia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Humanos , Imunossupressão , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico
12.
Biomed Res Int ; 2021: 6658070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485525

RESUMO

In light of the devastation caused by COVID-19, the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) and vaccine research and development (R&D) have been occupying a prominent position in the field of global health diplomacy (GHD). Most countries, international organizations, and charitable organizations have been engaged in the R&D of COVID-19 vaccines to ensure timely affordability and accessibility to all countries. Concomitantly, the World Trade Organization (WTO) provides some provisions and enforcements regarding copyrights, patents, trademarks, geographical indications, and industrial designs. Given these safeguards, it is considered that intellectual property rights (IPRs) have become major barriers to the affordability and accessibility of vaccines/medicines/technology, particularly to the developing/least developed countries. Realizing the gravity of the pandemic impact, as well as its huge population and size, India has elevated this issue in its global health diplomacy by submitting a joint proposal with South Africa to the World Trade Organization (WTO) for a temporary waiver of IPRs to ensure timely affordability and accessibility of COVID-19 medical products to all countries. However, the issue of the temporary waive off had become a geopolitical issue. Countries that used to claim per se as strong advocates of human rights, egalitarianism, and healthy democracy have opposed this proposal. In this contrasting milieu, this paper is aimed at examining how the TRIPS has become a barrier for developing countries' development and distribution of vaccines/technology; secondly, how India strategizes its role in the WTO in pursuant of its global health diplomacy? We conclude that the IPRs regime should not become a barrier to the accessibility/affordability of essential drugs and vaccines. To ensure access, India needs to get more engaged in GHD with all the involved global stakeholders to get strong support for their joint proposal. The developed countries that rejected/resisted the proposal can rethink their full support.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Diplomacia/métodos , Indústria Farmacêutica/métodos , Saúde Global , Acesso aos Serviços de Saúde , Direitos Humanos/métodos , Humanos , Índia , Saúde Pública/métodos , SARS-CoV-2/imunologia
14.
Front Immunol ; 12: 692937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497604

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising epitopes. Among them, ORF9b B-cell and T-cell epitopes are the most promising followed by M.ext and ORF3c epitopes. ORF9b40-48 (CD8+ T-cell epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell epitopes. Structure-based B-cell epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell epitopes (ORF9b65-69). ORF3c CD4+ T-cell epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell epitope (ORF3c14-22) have also been identified as the candidate epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext epitopes are finally shortlisted as potent epitopes. Mutation analysis has further revealed that the shortlisted potent uORF epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell epitopes identified here along with canonical ORF epitopes may aid in the design of a promising epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.


Assuntos
Antígenos Virais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , SARS-CoV-2/imunologia , Sequência de Aminoácidos/genética , Antígenos Virais/genética , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/uso terapêutico , Biologia Computacional , Proteínas do Nucleocapsídeo de Coronavírus/genética , Desenho de Fármacos , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Fases de Leitura Aberta/genética , Fases de Leitura Aberta/imunologia , SARS-CoV-2/genética , Análise de Sequência de Proteína , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia
17.
Front Immunol ; 12: 728513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484238

RESUMO

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.


Assuntos
Anticorpos/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/fisiopatologia , Adenoviridae/genética , Animais , Plaquetas/imunologia , Plaquetas/patologia , Vacinas contra COVID-19/imunologia , Modelos Animais de Doenças , Vetores Genéticos , Humanos , Camundongos , Ativação Plaquetária/imunologia , Fator Plaquetário 4 , Coelhos
18.
J Korean Med Sci ; 36(35): e250, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34490757

RESUMO

There are still no agreed guidelines on the vaccination of coronavirus disease 2019 (COVID-19) for previously infected patients. Here, we present two seropositive healthcare workers (HCWs) working in an isolation ward who recovered from COVID-19 in April 2020 and got vaccinated with BNT162b2 vaccine in March 2021. We have assessed the clinical course, vaccine-related adverse events, and antibody response after natural infection and after first and second dose vaccination. One of the two HCWs was asymptomatic during quarantine, but the other had mild upper respiratory infection symptoms 1 day before admission, and the symptoms continued for 9 days. There was no pneumonic infiltration in chest X-ray in both patients, and no COVID-19 specific treatment was administered. Total immunoglobulin antibody and neutralizing antibody to anti-spike protein receptor-binding domain of severe acute respiratory syndrome coronavirus 2 were confirmed to be present in both HCWs in blood tests performed at 2 weeks and 4 weeks after discharge. Antibody response to mRNA vaccination showed marked elevation after the first vaccination, which was 30-40 times higher than that of antibody titer after natural infection in each patient (83.2 U/mL vs. > 2,500 U/mL in patient 1; 61.6 U/mL vs. > 2,500 U/mL in patient 2). Signal inhibition rate of neutralizing antibodies was also increased to over 97%. Due to this increased effect, there was little difference in antibody levels after the first and second dose. Both patients 1 and 2 suffered more from adverse vaccine reactions after the second vaccination than from COVID-19 symptoms.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/sangue , COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Feminino , Pessoal de Saúde , Humanos , Vacinação
19.
mBio ; 12(4): e0114021, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465019

RESUMO

The recent emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant concern for public health worldwide. New variants have been classified either as variants of concern (VOCs) or variants of interest (VOIs) by the CDC (USA) and WHO. The VOCs include lineages such as B.1.1.7 (20I/501Y.V1 variant), P.1 (20J/501Y.V3 variant), B.1.351 (20H/501Y.V2 variant), and B.1.617.2. In contrast, the VOI category includes B.1.525, B.1.526, P.2, and B.1.427/B.1.429. The WHO provided the alert for last two variants (P.2 and B.1.427/B.1.429) and labeled them for further monitoring. As per the WHO, these variants can be reclassified due to their status at a particular time. At the same time, the CDC (USA) has marked these two variants as VOIs up through today. This article analyzes the evolutionary patterns of all these emerging variants, as well as their geographical distributions and transmission patterns, including the circulating frequency, entropy diversity, and mutational event diversity throughout the genomes of all SARS-CoV-2 lineages. The transmission pattern was observed highest in the B.1.1.7 lineage. Our frequency evaluation found that this lineage achieved 100% frequency in early October 2020. We also critically evaluated the above emerging variants mutational landscape and significant spike protein mutations (E484K, K417T/N, N501Y, and D614G) impacting public health. Finally, the effectiveness of vaccines against newly SARS-CoV-2 variants was also analyzed. IMPORTANCE Irrespective of the aggressive vaccination drive, the newly emerging multiple SARS-CoV-2 variants are causing havoc in several countries. As per the CDC (USA) and WHO, the VOCs include the B.1.1.7, P.1, B.1.351, and B.1.617.2 lineages, while the VOIs include the B.1.525, B.1.526, P.2, and B.1.427/B.1.429 lineages. This study analyzed the evolutionary patterns, geographical distributions and transmission patterns, circulating frequency, entropy diversity, and mutational event diversity throughout the genome of significant SARS-CoV-2 lineages. A higher transmission pattern was observed for the B.1.1.7 variant. The study also evaluated the mutational landscape and important spike protein mutations (E484K, K417T/N, N501Y, and D614G) of all of the above variants. Finally, a survey was performed on the efficacy of vaccines against these variants from the previously published literature. The results presented in this article will help design future countrywide pandemic planning strategies for the emerging variants, next-generation vaccine development using alternative wild-type antigens and significant viral antigens, and immediate planning for ongoing vaccination programs worldwide.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/transmissão , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Evolução Biológica , COVID-19/imunologia , COVID-19/patologia , Evolução Molecular , Genoma Viral/genética , Humanos , Filogenia , Saúde Pública , Glicoproteína da Espícula de Coronavírus/genética
20.
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34470866

RESUMO

Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV-like Sarbecovirus vaccine development.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/virologia , Macaca mulatta/imunologia , Nanopartículas/química , Receptores Virais/metabolismo , SARS-CoV-2/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Ferritinas/química , SARS-CoV-2/metabolismo , Linfócitos T/imunologia
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