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1.
EBioMedicine ; 77: 103904, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1867071

ABSTRACT

BACKGROUND: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. METHODS: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. FINDINGS: Standard BNT162b2 and CoronaVac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC50 and median frequencies of reactive CD4 subsets were consistently lower among CoronaVac-vaccinees than BNT162b2-vaccinees. CoronaVac did not induce measurable levels of nucleocapsid protein-specific IFN-γ+ CD4+ T or IFN-γ+ CD8+ T cells compared with unvaccinated. Against VOCs, NAb response rates and geometric mean IC50 titers against B.1.617.2 (Delta) and B.1.1.529 (Omicron) were significantly lower for CoronaVac (50%, 23.2 and 7.1%, <20) than BNT162b2 (94.1%, 131 and 58.8%, 35.0), respectively. Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among CoronaVac-vaccinees. INTERPRETATION: Our results indicate that vaccinees especially CoronaVac-vaccinees with significantly reduced NAbs may probably face higher risk to pandemic VOCs breakthrough infection. FUNDING: This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF and C1134-20GF); the Wellcome Trust (P86433); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.'s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19/epidemiology , COVID-19/prevention & control , Hong Kong/epidemiology , Humans , Immunity , SARS-CoV-2/genetics , Vaccination
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336861

ABSTRACT

Summary The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. In this study, we investigate public servants who had been vaccinated with two dose (82.7%) or three dose (14%) of either CoronaVac (CorV) or BNT162b2 (BNT). During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2×BNT 49.2% vs 3×BNT 16.6%, p <0.0001;2×CorV 48.6% vs 3×CoV 20.6%, p =0.003). The third heterologous vaccination showed the lowest incidence (2×CorV+1×BNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336250

ABSTRACT

Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. Although the third heterologous BNT162b2 vaccination after 2-dose CoronaVac generated higher neutralizing antibody responses than the third homologous CoronaVac booster, vaccine efficacy and corelates of immune protection against the major circulating Omicron BA.2 remains to be investigated. Methods: : We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 481 public servants who had been received with SARS-CoV-2 vaccines including two-dose BNT162b2 (2×BNT, n=169), three-dose BNT162b2 (2×BNT, n=175), two-dose CoronaVac (2×CorV, n=37), three-dose CoronaVac (3×CorV, n=68) and third-dose BNT162b2 following 2×CorV (2×CorV+1BNT, n=32). Humoral and cellular immune responses after three-dose vaccination were characterized and correlated with clinical characteristics of BA.2 infection. Results: : During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2×BNT 49.2% vs 3×BNT 16.6%, p<0.0001;2×CorV 48.6% vs 3×CoV 20.6%, p=0.003). The third heterologous vaccination showed the lowest incidence (2×CorV+1×BNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Conclusions: : Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.

4.
Front Immunol ; 12: 799896, 2021.
Article in English | MEDLINE | ID: covidwho-1662583

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.


Subject(s)
COVID-19/complications , Lymphopenia/complications , Lymphopenia/etiology , Mitochondrial Diseases/etiology , Adult , Aged , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/drug therapy , COVID-19/immunology , Female , Humans , Immunologic Memory/immunology , Ionomycin/therapeutic use , Lymphopenia/immunology , Male , Middle Aged , Mitochondria/immunology , Mitochondrial Diseases/immunology , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/therapeutic use , Polymethacrylic Acids/therapeutic use
6.
EBioMedicine ; 75: 103762, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1587929

ABSTRACT

BACKGROUND: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. METHODS: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FINDINGS: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. INTERPRETATION: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FUNDING: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunization, Secondary , Influenza Vaccines , SARS-CoV-2 , Vaccines, DNA , Administration, Intranasal , Animals , COVID-19/genetics , COVID-19/immunology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Disease Models, Animal , Dogs , Female , HEK293 Cells , Humans , Immunity, Mucosal , Influenza Vaccines/genetics , Influenza Vaccines/immunology , Madin Darby Canine Kidney Cells , Male , Mice , Mice, Inbred BALB C , Mice, Transgenic , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Vero Cells
8.
Immunity ; 53(4): 864-877.e5, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-693493

ABSTRACT

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.


Subject(s)
Betacoronavirus/pathogenicity , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Dendritic Cells/immunology , Diabetes Mellitus/immunology , Hypertension/immunology , Pneumonia, Viral/immunology , Adult , Aged , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/virology , COVID-19 , Convalescence , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Dendritic Cells/pathology , Dendritic Cells/virology , Diabetes Complications , Diabetes Mellitus/diagnosis , Diabetes Mellitus/virology , Disease Progression , Female , Humans , Hypertension/complications , Hypertension/diagnosis , Hypertension/virology , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Monocytes/immunology , Monocytes/pathology , Monocytes/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index
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