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Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model

Identifieur interne : 000607 ( PascalFrancis/Curation ); précédent : 000606; suivant : 000608

Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model

Auteurs : LANYING DU [République populaire de Chine, Hong Kong] ; GUANGYU ZHAO [République populaire de Chine] ; YUXIAN HE [République populaire de Chine, États-Unis] ; YAN GUO [République populaire de Chine] ; Bo-Jian Zheng [Hong Kong] ; SHIBO JIANG [États-Unis] ; YUSEN ZHOU [République populaire de Chine]

Source :

RBID : Pascal:07-0189645

Descripteurs français

English descriptors

Abstract

Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.
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C01 01    ENG  @0 Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.
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C07 04  X  ENG  @0 Lung disease @5 16
C07 04  X  SPA  @0 Pulmón patología @5 16
N21       @1 128
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Pascal:07-0189645

Le document en format XML

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<div type="abstract" xml:lang="en">Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.</div>
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<fA64 i1="01" i2="1">
<s0>Vaccine</s0>
</fA64>
<fA66 i1="01">
<s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>Development of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002A05F04</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Protéine</s0>
<s5>05</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Protein</s0>
<s5>05</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Proteína</s0>
<s5>05</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Immunoprotection</s0>
<s5>06</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Immunoprotection</s0>
<s5>06</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Inmunoprotección</s0>
<s5>06</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Modèle animal</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Animal model</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Modelo animal</s0>
<s5>07</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Sousunité</s0>
<s5>08</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Subunit</s0>
<s5>08</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Subunitad</s0>
<s5>08</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Vaccin</s0>
<s5>09</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Vaccine</s0>
<s5>09</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Vacuna</s0>
<s5>09</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Syndrome respiratoire aigu sévère</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Severe acute respiratory syndrome</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Síndrome respiratorio agudo severo</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Appareil respiratoire pathologie</s0>
<s5>13</s5>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Respiratory disease</s0>
<s5>13</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Aparato respiratorio patología</s0>
<s5>13</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Virose</s0>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Viral disease</s0>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Virosis</s0>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Infection</s0>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Infection</s0>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Infección</s0>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Poumon pathologie</s0>
<s5>16</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Lung disease</s0>
<s5>16</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Pulmón patología</s0>
<s5>16</s5>
</fC07>
<fN21>
<s1>128</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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