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1.
Nat Commun ; 14(1): 4174, 2023 07 13.
Article in English | MEDLINE | ID: mdl-37443074

ABSTRACT

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , BNT162 Vaccine , SARS-CoV-2 , COVID-19/prevention & control , Vaccination , Immunoglobulin Fc Fragments , Antibodies, Neutralizing , Antibodies, Viral
2.
bioRxiv ; 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35923313

ABSTRACT

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

3.
Mol Immunol ; 103: 63-70, 2018 11.
Article in English | MEDLINE | ID: mdl-30205305

ABSTRACT

The Surface Immunogenic Protein (SIP) of Group B Streptococcus (GBS) had been described as a good target for vaccine development. To date, SIP has been reported as a highly conserved protein, and in a mouse model it induces protection against lethal GBS challenge. Also, similar effects have been described by intranasal immunization with a SIP-based vaccine. In this study, we show the immune response induced by an oral SIP-based vaccine formulated on alum in a mouse model. Our vaccine can reduce vaginal GBS colonization and induce specific SIP-antibodies with opsonophagocytosis activities against GBS. Moreover, we observed the activation of T-cells producing IFN-γ, TNF-α, IL-10, IL-2, and increased expression of the transcription factor T-bet, suggesting a Th1-type humoral response. The oral SIP-based vaccine is a novel alternative in the development of a vaccine against GBS.


Subject(s)
Antigens, Bacterial/immunology , Streptococcal Infections/immunology , Streptococcus agalactiae/immunology , Vaccines/immunology , Vagina/immunology , Administration, Oral , Alum Compounds/administration & dosage , Alum Compounds/chemistry , Animals , Antibodies, Bacterial/immunology , Antigens, Bacterial/chemistry , Female , HL-60 Cells , Humans , Mice, Inbred C57BL , Streptococcal Infections/microbiology , Streptococcal Infections/prevention & control , Streptococcus agalactiae/drug effects , Streptococcus agalactiae/physiology , Vaccination/methods , Vaccines/administration & dosage , Vaccines/chemistry , Vagina/drug effects , Vagina/microbiology
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