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    Home > Active Ingredient News > Infection > Cell Res | Zhang Wenhong's team from Fudan University found that the third shot of new crown heterologous protein subunit vaccination is safe and effective

    Cell Res | Zhang Wenhong's team from Fudan University found that the third shot of new crown heterologous protein subunit vaccination is safe and effective

    • Last Update: 2021-12-05
    • Source: Internet
    • Author: User
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    Editor’s note iNature is China’s largest academic official account.
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    iNature as of October 2021, SARS-CoV-2 has infected more than 230 million people; promotion of vaccination can help build herd immunity against this epidemic
    .

    However, it has been reported that various vaccines have weakened antibody strength and reduced protective efficacy
    .

    A recent study reported that the third homologous vaccination showed satisfactory safety and higher immune response, including BNT162b2 mRNA vaccine, CoronaVac inactivated vaccine and BBIBP-CorV vaccine
    .

    In addition, the heterologous immunization of ChAdOx1 nCoV-19 and BNT162b2 induced a higher neutralizing activity compared with the two homologous doses of ChAdOx1 nCoV-19
    .

    So far, the effect of heterologous vaccination of recombinant protein subunit vaccines with two doses of inactivated vaccines has not been evaluated.
    Data along this line can provide further evidence for the formulation of future global heterologous vaccination promotion strategies
    .

    On November 23, 2021, Zhang Wenhong's team from Fudan University published an online publication titled "Recombinant protein subunit vaccine booster following two-dose inactivated vaccines enhanced anti-RBD responses and neutralizing titers against SARS-CoV-2 and Variants of Concern" in Cell Research.
    "The research paper, the study conducted this prospective, open-label study in a single center (the National Medical Center for Infectious Diseases (NMCID) Huashan Hospital, Shanghai, China), using two doses of inactivated whole virus vaccines (CoronaVac Or BBIBP-CorV) was administered 4-8 months after the previous primary vaccination to explore the safety and immunogenicity of the third booster vaccination with 25 μg protein subunit vaccine (ZF2001)
    .

    The study found that after two doses of inactivated whole virus vaccine were used as the “primer” injection, the third heterologous protein subunit vaccine was safe and highly immunogenic for healthy adults, which significantly increased the recall and increased Immune response to SARS-CoV-2 and its variants (the antibody level 14 days after the third dose has no significant difference between the schedules at different time intervals between the second and third injections)
    .

    The findings of this study provide important evidence for the establishment of a global heterologous vaccination promotion strategy against COVID-19 in the future
    .

    As of October 2021, SARS-CoV-2 has infected more than 230 million people; promotion of vaccination can help build herd immunity against this epidemic
    .

    However, various vaccines have been reported to have weakened antibody strength and reduced protective efficacy
    .

    With the circulatory mutation evading the immune response to some extent, these have led to a further strengthening of the vaccination controversy for recipients who have previously received “primary” vaccination
    .

    A recent study reported that the third homologous vaccination showed satisfactory safety and higher immune response, including BNT162b2 mRNA vaccine, CoronaVac inactivated vaccine and BBIBP-CorV vaccine
    .

    In addition, the heterologous immunization of ChAdOx1 nCoV-19 and BNT162b2 induced a higher neutralizing activity compared with the two homologous doses of ChAdOx1 nCoV-19
    .

    So far, the effect of heterologous vaccination of recombinant protein subunit vaccines with two doses of inactivated vaccines has not been evaluated.
    Data along this line can provide further evidence for the formulation of future global heterologous vaccination promotion strategies
    .

    The study conducted this prospective, open-label study in a single center (National Center for Infectious Diseases (NMCID) Huashan Hospital, Shanghai, China), using two doses of inactivated whole virus vaccines (CoronaVac or BBIBP-CorV) in healthy adults The administration was administered 4-8 months after the previous primary vaccination to explore the safety and immunogenicity of the third booster vaccination with 25 μg protein subunit vaccine (ZF2001)
    .

    The safety is evaluated by observing and analyzing adverse reactions, and the plasma replacement virus neutralization test (sVNT) is used to determine the neutralizing activity
    .

    In the baseline characteristics study, 71 participants in the boost group and 51 participants in the control group were included
    .

    The median age of the strengthening group was 28.
    00 (interquartile range (IQR) 25.
    00-44.
    30), and the control group was 26.
    00 (24.
    00-52.
    00) (P = 0.
    9880)
    .

    31 (43.
    70%) participants in the reinforcement group and 22 (43.
    10%) participants in the control group were male (P = 0.
    9540)
    .

    The body mass index of the booster group was slightly lower than that of the control group (22.
    30 vs 23.
    40, P = 0.
    0390)
    .

    As expected, the baseline immune response that "triggered" the two doses of inactivated vaccines 4-8 months after vaccination was comparable between the two groups
    .

    The median IFN-γ spot forming units (SFU) per million peripheral blood mononuclear cells (PBMC) for S1, S2, and N peptides were 5 (IQR 0-10), 0 (0-10), and 15 for the control group.
    (5-35), the strengthening groups are 10 (0-20), 5 (0-20) and 10 (0-25) respectively
    .

    Next, the study assessed the levels of neutralizing antibodies and anti-RBD antibodies: In the boost group, the geometric mean titers (GMT) of sVNT and pVNT were 18.
    19 (95% CI, 13.
    12-25.
    20) and 24.
    89 (20.
    63-), respectively.
    30.
    02), the median of total anti-RBD antibody and IgG levels were 8.
    47 (BAU)/mL (IQR 2.
    84-30.
    06) and 4.
    42 (BAU)/mL (2.
    09-12.
    41) in the analysis of immune response after booster vaccination , The increase in T cell response is generally weak
    .

    A significant increase in IFN-γ SFU per million PBMC was observed on the 14th day for the S2 peptide (10 vs.
    5, P = 0.
    0029), while no significant increase was found in the S1 and N peptide libraries
    .

    On the 14th day after booster vaccination, the level of pVNT was 75.
    58 times the baseline level
    .

    By the 14th day, the geometric mean titer (GMT) of sVNT increased to 503.
    47 times the baseline level, and on the 28th day it increased to 448.
    60 times the baseline GMT
    .

    The median anti-RBD antibody level and IgG level on day 14 were 8342.
    00 BAU/mL (IQR 3223.
    87-22350.
    00) and 1218.
    50 BAU/mL (869.
    75-1444.
    00), respectively, which were significantly higher than the baseline antibody level
    .

    By day 28, total anti-RBD antibody levels (4020.
    50 BAU/mL, 950.
    30-13050.
    00) and IgG levels (1140.
    50 BAU/mL, 786.
    60-1446.
    00) were slightly lower than the peak levels
    .

    The control group showed a stable low antibody titer
    .

    The antibody level at 14 days after the third administration did not differ significantly between the schedules with different intervals between the second and third injections (pVNT GMFR at a 4-month interval of 88.
    51; 5 months at 54.
    23, 6 Month is 109.
    71; 7 months is 70.
    19; 8 months is 84.
    25)
    .

    In addition, these booster doses induced at least a 70-fold increase in neutralizing GMT levels for the four variant pseudoviruses compared to baseline levels
    .

    In the booster group, 30 (42.
    30%) and 8 (11.
    30%) participants reported the required injection site and systemic adverse reactions within 3 days after the booster dose
    .

    The most common injection site and systemic adverse reactions are pain (20, 28.
    20%) and fatigue (6, 8.
    50%)
    .

    All adverse events were mild or moderate, and mostly disappeared 3 days after the booster vaccination
    .

    Only 4 (5.
    60%) and 1 (1.
    40%) participants reported new or persistent injection site adverse reactions from day 4 to 14 and day 15 to 28, 2 (2.
    80%) and 1 First name (1.
    40%) reported systemic adverse reactions during these periods
    .

    The study found that 4-8 months after the two vaccinations, the neutralizing GMT of the participants was still detectable, but it was lower than 14 days after the second vaccination (data from Huashan Hospital; ethics code : KY2021-041), IFN-γ produced by specific T cells can also be detected, but it is less than 12 weeks after the second vaccination
    .

    For all tested VOCs, the third booster dose after the previous two doses of inactivated vaccine can significantly recall and increase the functional B cell response by 27 to 75 times compared with 14 days after the second vaccination
    .

    These findings indicate that the "priming" of the two doses of inactivated vaccine can trigger long-lasting humoral and cellular immunity, which can be successfully recalled with a third dose of booster to provide protection against SARS-CoV-2 and its variants
    .

    The immune response to SARS-CoV-2 and variants of interest after boosting the recombinant protein subunit vaccine after two doses of inactivated vaccine (picture from Cell Research) This study showed satisfactory safety data, the previous test report The results of this study are similar to the 48% of mild or moderate adverse events in healthy adults during the entire plan of three-dose protein subunit vaccination
    .

    The study suggests that after two doses of inactivated vaccines are used as the primary immunization, the third dose of recombinant protein subunit vaccine as a booster may be safe for healthy adults aged 18-59
    .

    Since the participants of the study received different primary vaccines (two doses of CoronaVac or BBIBP-CorV), the study further conducted a subgroup analysis of participants who received different primary vaccines, and all subgroup analyses were consistent with the whole group analysis
    .

    In short, after two doses of inactivated whole virus vaccines were used as the "primer" injections, the third heterologous protein subunit vaccine was safe and highly immunogenic for healthy adults, which significantly recalled and increased the risk of SARS.
    -Immune response to CoV-2 and variants
    .

    The findings of this study provide important evidence for the establishment of a global heterologous vaccination promotion strategy against COVID-19 in the future
    .

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