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1.
J Virol ; 96(8): e0016922, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35343762

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.


Assuntos
Vacinas contra COVID-19 , Infecções por Coronavirus , Proteção Cruzada , Glicoproteína da Espícula de Coronavírus , Vacinas de Produtos Inativados , Enzima de Conversão de Angiotensina 2/genética , Animais , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Quirópteros , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteção Cruzada/imunologia , Humanos , Camundongos , Camundongos Transgênicos , Vírus da SARS/genética , Vírus da SARS/metabolismo , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Produtos Inativados/imunologia , Zoonoses Virais/prevenção & controle
2.
Signal Transduct Target Ther ; 7(1): 69, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241645

RESUMO

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the world. To investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain (RBD) (PS-RBD) and whole inactivated virus particle vaccine (IV) against the variant strains, in this study, rhesus macaques were immunized with PS-RBD or IV vaccine, followed by a Beta variant (B.1.351) challenge. Although neutralizing activity against the Beta variant was reduced compared with that against the prototype, the decreased viral load in both upper and lower respiratory tracts, milder pathological changes, and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque model. Furthermore, PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha, Beta, Delta, and Omicron variants in our study, though the neutralizing antibody (NAb) titers declined by varying degrees, demonstrating potential protection of PS-RBD against current circulating variants of concern (VOCs). Interestingly, although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant, it still showed reduction for viral load and significantly alleviated pathological change. Other correlates of vaccine-induced protection (CoP) like antibody-dependent cellular cytotoxicity (ADCC) and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Animais , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/farmacologia , Humanos , Macaca mulatta , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/farmacologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia
4.
Viruses ; 14(2)2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35215927

RESUMO

A new SARS-CoV-2 variant B.1.1.529 was named by the WHO as Omicron and classified as a Variant of Concern (VOC) on 26 November 2021. Because this variant has more than 50 mutations, including 30 mutations on the spike, it has generated a lot of concerns on the potential impacts of the VOC on COVID-19. Here through ELISA assays using the recombinant RBD proteins with sequences the same to that of SARS-CoV-2 WIV04 (lineage B.1), the Delta variant and the Omicron variant as the coating antigens, the binding capabilities between the RBDs and the antibodies in COVID-19 convalescent sera and vaccine sera after two doses of the inactivated vaccine produced by Sinopharm WIBP are compared with each other. The results showed that the Omicron variant may evade antibodies induced by the ancestral strain and by the inactivated vaccine, with significant reduction in the binding capability of its RBD much greater than that of the Delta variant.


Assuntos
Anticorpos Antivirais/metabolismo , Sítios de Ligação de Anticorpos/fisiologia , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Convalescença , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Humanos , Evasão da Resposta Imune , Mutação , Testes de Neutralização , Vacinas de Produtos Inativados/imunologia
5.
J Virol ; 96(6): e0195921, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35107371

RESUMO

Seasonal influenza vaccination takes into account primarily hemagglutinin (HA)-specific neutralizing antibody responses. However, the accumulation of substitutions in the antigenic regions of HA (i.e., antigenic drift) occasionally results in a mismatch between the vaccine and circulating strains. To prevent poor vaccine performance, we investigated whether an antigenically matched neuraminidase (NA) may compensate for reduced vaccine efficacy due to a mismatched HA. Ferrets were vaccinated twice with adjuvanted split inactivated influenza vaccines containing homologous HA and NA (vacH3N2), only homologous HA (vacH3N1), only homologous NA (vacH1N2), heterologous HA and NA (vacH1N1), or phosphate-buffered saline (vacPBS), followed by challenge with H3N2 virus (A/Netherlands/16190/1968). Ferrets vaccinated with homologous HA (vacH3N2 and vacH3N1) displayed minimum fever and weight loss compared to vacH1N1 and vacPBS ferrets, while ferrets vaccinated with NA-matched vacH1N2 displayed intermediate fever and weight loss. Vaccination with vacH1N2 further led to a reduction in virus shedding from the nose and undetectable virus titers in the lower respiratory tract, similarly to when the homologous vacH3N2 was used. Some protection was observed upon vacH1N1 vaccination, but this was not comparable to that observed for vacH1N2, again highlighting the important role of NA in vaccine-induced protection. These results illustrate that NA antibodies can prevent severe disease caused by influenza virus infection and that an antigenically matched NA in seasonal vaccines might prevent lower respiratory tract complications. This underlines the importance of considering NA during the yearly vaccine strain selection process, which may be particularly beneficial in seasons when the HA component of the vaccine is mismatched. IMPORTANCE Despite the availability of vaccines, influenza virus infections continue to cause substantial morbidity and mortality in humans. Currently available influenza vaccines take primarily the hemagglutinin (HA) into account, but the highly variable nature of this protein as a result of antigenic drift has led to a recurrent decline in vaccine effectiveness. While the protective effect of neuraminidase (NA) antibodies has been highlighted by several studies, there are no requirements with regard to quantity or quality of NA in licensed vaccines, and NA immunity remains largely unexploited. Since antigenic changes in HA and NA are thought to occur asynchronously, NA immunity could compensate for reduced vaccine efficacy when drift in HA occurs. By matching and mismatching the HA and NA components of monovalent split inactivated vaccines, we demonstrated the potential of NA immunity to protect against disease, virus replication in the lower respiratory tract, and virus shedding in the ferret model.


Assuntos
Vírus da Influenza A , Vacinas contra Influenza , Neuraminidase , Infecções por Orthomyxoviridae , Animais , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Furões , Hemaglutininas/imunologia , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/normas , Neuraminidase/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Estações do Ano , Vacinas de Produtos Inativados/imunologia
7.
Viruses ; 14(2)2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35215904

RESUMO

The aim of the report was to present the circulation of BVDV (bovine viral diarrhea virus) in the cattle population and determine the cause of the failure of vaccination failure leading to the birth of the PI (persistently infected) calf. The case study was carried out at the BVDV-free animal breeding center and cattle farm, where the vaccination program against BVDV was implemented in 2012, and each newly introduced animal was serologically and virologically tested for BVDV. In this case, a blood sample was taken from a 9-month-old breeding bull. Positive RT-PCR and negative ELISA serology results were obtained. The tests were repeated at 2-week intervals, and the results confirmed the presence of the virus and the absence of specific antibodies, i.e., persistent infection. Additionally, sequencing and phylogenetic analysis were performed, and the BVDV-1d subgenotype was detected. The results of this study showed that pregnant heifers and cows that are vaccinated multiple times with the killed vaccine containing BVDV-1a may not be fully protected against infection with other subgenotypes of BVDV, including their fetuses, which can become PI calves.


Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Vírus da Diarreia Viral Bovina/imunologia , Doenças Fetais/prevenção & controle , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Doença das Mucosas por Vírus da Diarreia Viral Bovina/sangue , Doença das Mucosas por Vírus da Diarreia Viral Bovina/embriologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos , Vírus da Diarreia Viral Bovina/classificação , Vírus da Diarreia Viral Bovina/genética , Vírus da Diarreia Viral Bovina/isolamento & purificação , Feminino , Doenças Fetais/virologia , Masculino , /virologia , Filogenia , Gravidez , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/genética , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/genética
8.
Viruses ; 14(2)2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35215870

RESUMO

This study compared the immunogenicity of inactivated SARS-CoV-2 vaccines between people living with HIV (PLWH) and HIV-negative individuals. We recruited 120 PLWH and 53 HIV-negative individuals aged 18-59 years who had received an inactivated SARS-CoV-2 vaccine in two Chinese cities between April and June 2021. Blood samples were tested for immunogenicity of the inactivated SARS-CoV-2 vaccines. The prevalence and severity of adverse events associated with SARS-CoV-2 vaccines were similar between PLWH and HIV-negative individuals. The seropositivity of neutralizing activity against authentic SARS-CoV-2, of the total amount of antibody (total antibody) and of S-IgG were 71.3%, 81.9%, and 92.6%, respectively, among fully vaccinated PLWH. Among all participants, PLWH had lower neutralizing activity, total antibody, S-IgG, and T-cell-specific immune response levels, compared to HIV-negative individuals, after controlling for types of vaccine, time interval between first and second dose, time after receiving the second dose, and sociodemographic factors. PLWH with a longer interval since HIV diagnosis, who received their second dose 15-28 days prior to study commencement, and who had an interval of ≥21 days between first and second dose had higher neutralizing activity levels. The immunogenicity of the inactivated SARS-CoV-2 vaccines was lower among PLWH as compared to HIV-negative individuals. Vaccination guideline specific for PLWH should be developed.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , Infecções por HIV/epidemiologia , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Adulto Jovem
9.
PLoS One ; 17(2): e0263468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35108321

RESUMO

BACKGROUND: Mass vaccination is the key element in controlling current COVID-19 pandemic. Studies comparing immunogenicity of different COVID-19 vaccines are largely lacking. We aimed at measuring anti-S antibody (Ab) levels in individuals fully vaccinated with BNT162b2, BBIBP-CorV and Gam-COVID-Vac, as well as in COVID-19 convalescents. METHODS: In this cross-sectional study, serum was collected from 400 age- and sex-matched participants, 100 fully vaccinated with BNT162b2, 100 with BBIBP-CorV and 100 with Gam-COVID-Vac on the 28th day after the second vaccine dose, and 100 recovered from COVID-19 at least 28 days after symptom(s) resolution. Sera were analyzed using the LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy). Wilcoxon rank-sum or Kruskal-Wallis tests was used for comparison of Ab levels. RESULTS: Highest mean value (210.11, SD = 100.42) was measured in the BNT162b2 group, followed by Gam-COVID-Vac (171.11, SD = 120.69) and BBIBP-CorV (68.50, SD = 72.78) AU/mL (p<0.001). Significant differences in antibody levels were found between BNT162b2 and BBIBP-CorV (p<0.001), BNT162b2 and Gam-COVID-Vac (p = 0.001), as well as BBIBP-CorV and Gam-COVID-Vac groups (p<0.001). Percentage of seropositive was 81% in the convalescent group, 83% in BBIBP-CorV vaccinated and 100% in BNT162b2 and Gam-COVID-Vac. When comparing measured antibody levels in vaccinated to those in COVID-19 recovered, significantly higher antibody levels were found for vaccinated with BNT162b2 (p<0.001), and with Gam-COVID-Vac (p<0.001), while for BBIBP-CorV there was no statistically significant difference (p = 0.641). CONCLUSIONS: All three investigated vaccines, BNT162b2, BBIBP-CorV and Gam-COVID-Vac, provide robust immune response 28 days after the second dose of vaccine, in the majority of participants. All individuals vaccinated with BNT162b2 and Gam-COVID-Vac seroconverted, while in vaccinated with BBIBP-CorV and COVID-19 recovered seroconversion rates were lower. Although less potent compared to other two vaccines, immune response after BBIBP-CorV was similar to response measured in convalescents. Challenge still remains to examine dynamics and durability of immunoprotection.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/imunologia , COVID-19/terapia , Resultado do Tratamento , Adulto , Anticorpos/análise , Anticorpos/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , Vacinas contra COVID-19/imunologia , Convalescença , Estudos Transversais , Feminino , Humanos , Imunidade/imunologia , Imunidade Inata/imunologia , Imunogenicidade da Vacina/imunologia , Imunoglobulina G/análise , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Sérvia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologia
10.
Front Immunol ; 13: 829665, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154152

RESUMO

Background: Understanding the long-term kinetic characteristics of SARS-CoV-2 antibodies and the impact of inactivated vaccines on SARS-CoV-2 antibodies in convalescent patients can provide information for developing and improving vaccination strategies in such populations. Methods: In this cohort, 402 convalescent patients who tested positive for SARS-CoV-2 by RT-PCR from 1 January to 22 June 2020 in Jiangsu, China, were enrolled. The epidemiological data included demographics, symptom onset, and vaccination history. Blood samples were collected and tested for antibody levels of specific IgG, IgM, RBD-IgG, S-IgG, and neutralizing antibodies using a the commercial magnetic chemiluminescence enzyme immunoassay. Results: The median follow-up time after symptom onset was 15.6 months (IQR, 14.6 to 15.8). Of the 402 convalescent patients, 44 (13.84%) received an inactivated vaccine against COVID-19. A total of 255 (80.19%) patients were IgG-positive and 65 (20.44%) were IgM-positive. The neutralizing antibody was 83.02%. Compared with non-vaccinated individuals, the IgG antibody levels in vaccinated people were higher (P=0.007). Similarly, antibody levels for RBD-IgG, S-IgG, and neutralizing antibodies were all highly increased in vaccinated individuals (P<0.05). IgG levels were significantly higher after vaccination than before vaccination in the same population. IgG levels in those who received 'single dose and ≥14d' were similar to those with two doses (P>0.05). Similar conclusions were drawn for RBD-IgG and the neutralizing antibody. Conclusion: 15.6 months after symptom onset, the majority of participants remained positive for serum-specific IgG, RBD-IgG, S-IgG, and neutralizing antibodies. For convalescent patients, a single dose of inactivated vaccine against COVID-19 can further boost antibody titres.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , China , Estudos de Coortes , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
11.
Nat Med ; 28(2): 401-409, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35087233

RESUMO

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 (COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial ( NCT04892459 ). Adults who had received two doses of CoronaVac in the past 3-6 months were vaccinated with Convidecia (n = 96) or CoronaVac (n = 102). Adults who had received one dose of CoronaVac in the past 1-3 months were also vaccinated with Convidecia (n = 51) or CoronaVac (n = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , SARS-CoV-2/imunologia , Adenoviridae/imunologia , Adolescente , Adulto , COVID-19/imunologia , COVID-19/prevenção & controle , China , Feminino , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Reação no Local da Injeção/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacinação , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
13.
Future Oncol ; 18(10): 1235-1244, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35081732

RESUMO

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).


Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Neoplasias/imunologia , SARS-CoV-2/imunologia , Vacinação , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
14.
Emerg Microbes Infect ; 11(1): 477-481, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35034583

RESUMO

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera from convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists seven of eight authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunização Secundária , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/imunologia , Anticorpos Monoclonais/imunologia , Vacinas contra COVID-19/administração & dosagem , Epitopos/imunologia , Humanos , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Vacinas de Produtos Inativados/administração & dosagem
15.
Cell Rep ; 38(1): 110184, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34986349

RESUMO

MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.


Assuntos
Vacinas Bacterianas/imunologia , Imunidade nas Mucosas/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Mucosa Respiratória/imunologia , Infecções Respiratórias/prevenção & controle , Administração Intranasal , Animais , Anticorpos Antivirais/imunologia , Bactérias/imunologia , Vacinas Bacterianas/administração & dosagem , Candidíase/prevenção & controle , Linhagem Celular , Chlorocebus aethiops , Citocinas/biossíntese , Humanos , Vírus da Influenza A/imunologia , Células L , Pulmão/imunologia , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
16.
Cancer Invest ; 40(1): 26-34, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34634986

RESUMO

OBJECTIVE: To evaluate the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine in cancer patients. MATERIAL AND METHOD: 364 cancer patients who received two doses of vaccine were enrolled. The presence of SARS-CoV-2 anti-Spike protein IgG and neutralizing antibody 2 months following vaccination were measured by ELIZA. RESULTS: Injection site pain and fever were the most common local and systemic side effects. The overall seroconversion rate was 86.9% that was lower in older age, those with hematological malignancies and chemotherapy receivers. CONCLUSION: The result of study confirmed the safety and short-term efficacy of inactivated vaccine in patients with malignancies.


Assuntos
Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , Neoplasias/tratamento farmacológico , Vacinas de Produtos Inativados/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Lancet Infect Dis ; 22(2): 196-208, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34536349

RESUMO

BACKGROUND: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years. METHODS: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 µg, 4 µg, or 8 µg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing. FINDINGS: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination. INTERPRETATION: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 µg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/normas , COVID-19/prevenção & controle , Adolescente , Vacinas contra COVID-19/administração & dosagem , Criança , Pré-Escolar , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Masculino , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/normas
19.
Int Immunopharmacol ; 102: 108383, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34824035

RESUMO

BACKGROUNDS: To date, the effects of SARS-CoV-2 vaccines on people living with HIV (PLWH) were mainly focused on messenger RNA (mRNA) and adenovirus vector-based vaccines, and little is known about the effects of inactivated virus-based vaccine. This study was designed to determine the effects of inactivated SARS-CoV-2 vaccines on PLWH. METHODS: Twenty-four HIV-positive individuals and 24 healthy donors (HD) were respectively recruited from Malipo Country People's Hospital and community in Kunming city. Enumeration of lymphocyte and CD4+CD45RO+ memory T cells were evaluated by flow cytometry. Competitive ELISA was used to measure the level of Anti-SARS-CoV-2 neutralization antibody. Spearman or Pearson correlation analysis was used to analyze the relationship between laboratory indicators and neutralization antibodies in PLWH. T-cell responses (Th1, Th2, Th17, Treg) and intracellular expression of cytokines (IL-2 and TNF-α) in CD4 or CD8 were induced by spike protein in SARS-CoV-2 (SARS-2-S) and further measured by intracellular staining. RESULTS: CD4, B cells, CD4+CD45RO+ memory T cells in peripheral blood of PLWH are dramatically decreased in comparison with HD. Importantly, PLWH display comparable neutralizing antibody positive rate to HD after inoculation with inactivated SARS-CoV-2 vaccine. However, PLWH showed weaker responses to vaccines exhibited by lower levels of neutralizing antibodies. Correlation analysis shows that this is possibly caused by low number of CD4 and B cells. Furthermore, SARS-2-S-induced Th2 and Th17 responses are also decreased in PLWH, while no influences on Treg and other cytokines (IL-2, TNF-α and IFN-γ) observed. CONCLUSIONS: PLWH and HD have comparable neutralizing antibodies positive rates, but PLWH display weaker responses to inactivated SARS-CoV-2 vaccines in magnitude, which suggests that a booster dose or dose adjustment are required for HIV-infected individuals, especially for those with lower counts of CD4 T and B cells.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Infecções por HIV/imunologia , Vacinas de Produtos Inativados/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Voluntários Saudáveis , Humanos , Imunogenicidade da Vacina , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Células Th17/imunologia , Células Th2/imunologia , Vacinas de Produtos Inativados/administração & dosagem
20.
J Med Virol ; 94(4): 1442-1449, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34783049

RESUMO

Effective vaccines are essential for controlling the coronavirus disease 2019 (COVID-19) pandemic. CoronaVac, which is an inactivated virus vaccine, was the first imported COVID-19 vaccine in Thailand. To investigate the safety and immunogenicity of CoronaVac within the Thai population, we conducted a prospective cohort study among health care workers aged 18-59 years, who received a 2-dose regimen of CoronaVac 21 days apart between March and April 2021 at the hospital in Samut Sakhon, Thailand. We recruited 185 participants with a mean age of 32 years. Total antibodies against receptor-binding domain (RBD) and immunoglobulin G (IgG) against nucleocapsid (N) protein of SARS-CoV-2 were tested. Total antibodies against RBD were negative before immunization. One volunteer was positive for N, although negative for the RBD antibodies. The seroconversion rate of total antibodies against RBD after the first CoronaVac dose was 67% with a Geometric mean concentration (GMC) of 1.98 U/ml. Following CoronaVac dose 2, the seroconversion rate increased to 100% with a GMC of 92.9 U/ml. The seroconversion rates of IgG against N protein were 1% after dose 1 and 62.8% after dose 2. The overall incidence of adverse reactions was 59.5%. Injection-site pain was the most common local adverse event (52.4%), while myalgia was the most common systemic adverse event (31.9%). No serious adverse events were observed. A 0-21 days, 2-dose CoronaVac regimen appears safe, inducing a satisfactory response compared with convalescent serum obtained 4-6 weeks postnatural infection. Antibody responses after 2-dose CoronaVac were comparable to the convalescent plasma but waned rapidly after 3 months. Therefore, we recommend 2-dose CoronaVac administration with possible booster doses.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Pessoal de Saúde , Humanos , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Soroconversão , Tailândia/epidemiologia , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Adulto Jovem
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