scholarly journals Broad anti-SARS-CoV-2 antibody immunity induced by heterologous ChAdOx1/mRNA-1273 prime-boost vaccination

2021 ◽  
Author(s):  
Chengzi I Kaku ◽  
Elizabeth Champney ◽  
Johan Normark ◽  
Carl E Johnson ◽  
Clas Ahlm ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Molecular Basis ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Binding Affinities ◽  
Booster Immunization ◽  
Boost Vaccination ◽  
Immunization Strategies ◽  
Boost Immunization

Heterologous prime-boost immunization strategies have the potential to augment COVID-19 vaccine efficacy and address ongoing vaccine supply challenges. Here, we longitudinally profiled SARS-CoV-2 spike (S)-specific serological and memory B cell (MBC) responses in individuals receiving either homologous (ChAdOx1:ChAdOx1) or heterologous (ChAdOx1:mRNA-1273) prime-boost vaccination. Heterologous mRNA booster immunization induced significantly higher serum neutralizing antibody and MBC responses compared to homologous ChAdOx1 boosting. Specificity mapping of circulating S-specific B cells revealed that mRNA-1273 booster immunization dramatically immunofocused ChAdOx1-primed responses onto epitopes expressed on prefusion-stabilized S. Monoclonal antibodies isolated from mRNA-1273-boosted participants displayed higher binding affinities and increased breadth of reactivity against variants of concern (VOCs) relative to those isolated from ChAdOx1-boosted participants. Overall, the results provide fundamental insights into the B cell response induced by ChAdOx1 and a molecular basis for the enhanced immunogenicity observed following heterologous mRNA booster vaccination.

Comparison of Injected and Oral Polio Vaccine for Booster Immunization During the 1979 Polio Outbreak in Lancaster County, Pennsylvania

1981 ◽  
Vol 2 (5) ◽  
pp. 377-379
Author(s):  
Robert G. Doe ◽  
Bruce Kleger ◽  
John L. Randall
Keyword(s):  
Booster Vaccination ◽  
Oral Polio Vaccine ◽  
Neutralizing Antibody ◽  
Igg Antibody ◽  
Booster Immunization ◽  
Lancaster County ◽  
Polio Vaccine ◽  
Before And After ◽  
Antibody Titers ◽  
Better Than

AbstractDuring a 1979 outbreak of poliomyelitis in Lancaster County, Pennsylvania, we investigated the neccessity for and the response to booster vaccination of hospital personnel. The immune response of hospital employees who received booster injections of Salk vaccine (n=38) was compared with that of residents in the surrounding community who received Sabin trivalent OPV boosters (n=43). Serum neutralizing antibody titers to the three polio serotypes were measured before and after booster immunization. Results indicated that 38% of the subjects in both groups had low initial antibody titers. Salk vaccine was in all circumstances as effective or better than Sabin vaccine in increasing neutralizing IgG antibody titers [Infect Control 1981; 2(5):377-379.]

scholarly journals Impaired Neutralizing Antibody Response to COVID-19 mRNA Vaccines in Cancer Patients

2021 ◽  
Author(s):  
Cong Zeng ◽  
John P. Evans ◽  
Sarah Reisinger ◽  
Jennifer Woyach ◽  
Christina Liscynesky ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Cancer Patients ◽  
Neutralizing Antibody ◽  
Lymphocytic Leukemia ◽  
Cell Therapies ◽  
Cancer Breast ◽  
Immunization Strategies ◽  
Hematological Cancers ◽  
Hodgkin's Lymphomas

There is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin's lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50 levels, with 50-60% of them below the detection limit; (3) mean NT50 levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50 levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.

scholarly journals Slow delivery immunization enhances HIV neutralizing antibody and germinal center responses via modulation of immunodominance

2018 ◽  
Author(s):  
Kimberly M. Cirelli ◽  
Diane G. Carnathan ◽  
Bartek Nogal ◽  
Oscar L. Rodriguez ◽  
Jacob T. Martin ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Reference Sequence ◽  
Fine Needle Aspirates ◽  
Immunization Strategies ◽  
Gene Usage ◽  
Hiv 1

SUMMARYThe observation that humans can produce broadly neutralizing antibodies (bnAbs) against HIV-1 has generated enthusiasm about the potential for a bnAb vaccine against HIV-1. Conventional immunization strategies will likely be insufficient for the development of a bnAb HIV vaccine and vaccines to other difficult pathogens, due to the significant immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. Using longitudinal lymph node fine needle aspirates, we found that two independent methods of slow delivery immunization of rhesus macaques (RM) resulted in larger GCs, more robust and sustained GC Tfh cell responses, and GC B cells with improved Env-binding, which correlated with the development of ~20 to 30-fold higher titers of tier 2 HIV-1 nAbs. Using a new RM genomic immunoglobulin loci reference sequence, we identified differential IgV gene usage between slow delivery immunized and conventional bolus immunized animals. The most immunodominant IgV gene used by conventionally immunized animals was associated with many GC B cell lineages. Ab mapping of those GC B cell specificities demonstrated targeting of an immunodominant non-neutralizing trimer base epitope, while that response was muted in slow delivery immunized animals. Thus, alternative immunization strategies appear to enhance nAb development by altering GCs and modulating immunodominance of non-neutralizing epitopes.

scholarly journals Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cong Zeng ◽  
John P. Evans ◽  
Sarah Reisinger ◽  
Jennifer Woyach ◽  
Christina Liscynesky ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Cancer Patients ◽  
Neutralizing Antibody ◽  
Lymphocytic Leukemia ◽  
Cell Therapies ◽  
Cancer Breast ◽  
Immunization Strategies ◽  
Hematological Cancers ◽  
Hodgkin's Lymphomas

AbstractThere is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin’s lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50 levels, with 50-60% of them below the detection limit; (3) mean NT50 levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50 levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.

scholarly journals Recombinant BCG-Prime and DNA-Boost Immunization Confers Mice with Enhanced Protection against Mycobacterium kansasii

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1260
Author(s):  
Shihoko Komine-Aizawa ◽  
Satoru Mizuno ◽  
Kazuhiro Matsuo ◽  
Takahiro Namiki ◽  
Satoshi Hayakawa ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Multidrug Resistant ◽  
Mycobacterium Kansasii ◽  
Booster Immunization ◽  
Boost Vaccination ◽  
Antigen 85B ◽  
Boost Immunization ◽  
Potential Alternative ◽  
Mouse Lungs

The incidence of infections with nontuberculous mycobacteria (NTM) has been increasing worldwide. The emergence of multidrug-resistant NTM is a serious clinical concern, and a vaccine for NTM has not yet been developed. We previously developed a new recombinant Bacillus Calmette–Guérin (rBCG) vaccine encoding the antigen 85B (Ag85B) protein of Mycobacterium kansasii—termed rBCG-Mkan85B—which was used together with a booster immunization with plasmid DNA expressing the same M. kansasii Ag85B gene (DNA-Mkan85B). We reported that rBCG-Mkan85B/DNA-Mkan85B prime–boost immunization elicited various NTM strain-specific CD4+ and CD8+ T cells and induced Mycobacterium tuberculosis-specific immunity. In this study, to investigate the protective effect against M. kansasii infection, we challenged mice vaccinated with a rBCG-Mkan85B or rBCG-Mkan85B/DNA-Mkan85B prime–boost strategy with virulent M. kansasii. Although BCG and rBCG-Mkan85B immunization each suppressed the growth of M. kansasii in the mouse lungs, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination reduced the bacterial burden more significantly. Moreover, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination induced antigen-specific CD4+ and CD8+ T cells. Our data suggest that rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination effectively enhances antigen-specific T cells. Our novel rBCG could be a potential alternative to clinical BCG for preventing various NTM infections.

scholarly journals Prime-boost vaccination with plasmid DNA followed by recombinant vaccinia virus expressing BgGARP induced a partial protective immunity to inhibit Babesia gibsoni proliferation in dogs

2013 ◽  
Vol 58 (4) ◽  
Author(s):  
Shinuo Cao ◽  
Ahmed Mousa ◽  
Gabriel Aboge ◽  
Ketsarin Kamyingkird ◽  
Mo Zhou ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Protective Immunity ◽  
Recombinant Vaccinia Virus ◽  
Babesia Gibsoni ◽  
Partial Protection ◽  
Recombinant Vaccinia ◽  
Booster Immunization ◽  
Boost Vaccination ◽  
Boost Immunization ◽  
High Level

AbstractA heterologous prime-boost vaccination regime with DNA and recombinant vaccinia virus (rvv) vectors expressing relevant antigens has been shown to induce effective immune responses against several infectious pathogens. In this study, we describe the effectiveness of the prime-boost strategy by immunizing dogs with a recombinant plasmid followed by vaccinia virus, both of which expressed the glutamic acid-rich protein (BgGARP) of Babesia gibsoni. The dogs immunized with the prime-boost regime developed a significantly high level of specific antibodies against BgGARP when compared with the control groups. The antibody level was strongly increased after a booster immunization with a recombinant vaccinia virus. Two weeks after the booster immunization with a recombinant vaccinia virus expressing BgGARP, the dogs were challenged with B. gibsoni parasite. The dogs immunized with the prime-boost regime showed partial protection, manifested as a significantly low level of parasitemia. These results indicated that this type of DNA/rvv prime-boost immunization approach may have use against B. gibsoni infection in dogs.

scholarly journals Antibody-based therapy of leukaemia

2009 ◽  
Vol 11 ◽  
Author(s):  
John C. Morris ◽  
Thomas A. Waldmann
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Gemtuzumab Ozogamicin ◽  
Cell Leukaemia ◽  
Target Cells ◽  
Immune Effector ◽  
Effector Cells ◽  
Prolymphocytic Leukaemia ◽  
Immune Effector Cells

Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies – the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab – are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.

Monoclonal antibodies that block adhesion of B cell progenitors to bone marrow stromain vitro prevent B cell differentiationin vivo

1991 ◽  
Vol 21 (9) ◽  
pp. 2043-2049 ◽  
Author(s):  
Beat A. Imhof ◽  
Claude Schlienger ◽  
Klaus Handloser ◽  
Barbara Hesse ◽  
Michaela Slanicka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
B Cell
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