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1.
EBioMedicine ; 77: 103902, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35228013

RESUMO

BACKGROUND: There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. METHODS: In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). FINDINGS: We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens. INTERPRETATION: Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC. FUNDING: This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2/genética
2.
Hum Vaccin Immunother ; 14(6): 1524-1529, 2018 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-29359991

RESUMO

The function of adjuvant in maintaining the long-term immune response to Typhoid conjugate vaccine (TCV) was evaluated in. Two TCV products, Vi-DT and Vi-TT, were formulated in either aluminum phosphate (AlPO4) or aluminum hydroxide (AlOH) as adjuvants and TCV formulated in phosphate buffer saline were used as controls. In each case, a group of Balb/c mice was injected intramuscularly with two doses of the formulated vaccine at two-week intervals. The anti-Vi IgG responses were monitored by Enzyme-Linked Immunosorbent Assay and the levels of CD4+ T-cells expressing cytokine were characterized using intracellular cytokine staining. All mice immunized by TCV formulated in adjuvant elicited anti-Vi response to a higher level than the group receiving TCV formulated in PBS. The extent of adsorption of TCV in AlOH was greater than that in AlPO4, and this finding correlated well with the observation that the mice immunized with two doses of Vi-DT(AlOH) elicited anti-Vi IgG to a level higher than that seen with Vi-DT(AlPO4). The mice primed with Vi-TT(AlOH) produced lower anti-Vi IgG (25.901 GM) compared to those receiving Vi-TT(AlPO4) (49.219 GM). However, after the second injection, the former raised the antibody level significantly to 137.008 GM while the latter provided a value of only 104.966 GM. The groups of mice vaccinated by TCV formulated in AlOH expressed IL4 at higher levels than the other groups, which correlated positively with the high Anti-Vi IgG in these animals. In conclusion, AlOH could be recommended as an effective adjuvant for TCV to provide a long-term immune response.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/administração & dosagem , Anticorpos Antibacterianos/sangue , Linfócitos T CD4-Positivos/imunologia , Salmonella typhi/imunologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/imunologia , Animais , Citocinas/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina G/sangue , Injeções Intramusculares , Masculino , Camundongos Endogâmicos BALB C , Vacinas Tíficas-Paratíficas/administração & dosagem
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