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  1. Article ; Online: Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant.

    Nesamari, Rofhiwa / Omondi, Millicent A / Baguma, Richard / Höft, Maxine A / Ngomti, Amkele / Nkayi, Anathi A / Besethi, Asiphe S / Magugu, Siyabulela F J / Mosala, Paballo / Walters, Avril / Clark, Gesina M / Mennen, Mathilda / Skelem, Sango / Adriaanse, Marguerite / Grifoni, Alba / Sette, Alessandro / Keeton, Roanne S / Ntusi, Ntobeko A B / Riou, Catherine /
    Burgers, Wendy A

    Cell host & microbe

    2024  Volume 32, Issue 2, Page(s) 162–169.e3

    Abstract: Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross- ... ...

    Abstract Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection. Spike-specific T cells are highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant nucleocapsid and membrane-specific T cells are detectable in most participants. The bulk of SARS-CoV-2-specific T cell responses have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Memory T Cells ; Pandemics ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2024-01-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2023.12.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity.

    Benede, Ntombi S B / Tincho, Marius B / Walters, Avril / Subbiah, Vennesa / Ngomti, Amkele / Baguma, Richard / Butters, Claire / Mennen, Mathilda / Skelem, Sango / Adriaanse, Marguerite / van Graan, Strauss / Balla, Sashkia R / Moyo-Gwete, Thandeka / Moore, Penny L / Botha, Maresa / Workman, Lesley / Zar, Heather J / Ntusi, Ntobeko A B / Zühlke, Liesl /
    Webb, Kate / Riou, Catherine / Burgers, Wendy A / Keeton, Roanne S

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South ... ...

    Abstract SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children.
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.16.23290059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation.

    Karim, Farina / Riou, Catherine / Bernstein, Mallory / Jule, Zesuliwe / Lustig, Gila / van Graan, Strauss / Keeton, Roanne S / Upton, Janine-Lee / Ganga, Yashica / Khan, Khadija / Reedoy, Kajal / Mazibuko, Matilda / Govender, Katya / Thambu, Kershnee / Ngcobo, Nokuthula / Venter, Elizabeth / Makhado, Zanele / Hanekom, Willem / von Gottberg, Anne /
    Hoque, Monjurul / Karim, Quarraisha Abdool / Abdool Karim, Salim S / Manickchund, Nithendra / Magula, Nombulelo / Gosnell, Bernadett I / Lessells, Richard J / Moore, Penny L / Burgers, Wendy A / de Oliveira, Tulio / Moosa, Mahomed-Yunus S / Sigal, Alex

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2360

    Abstract: SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in ... ...

    Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; HIV Infections/drug therapy ; Antibodies, Neutralizing ; Antibodies, Viral
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2024-03-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46673-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comparing the immune abnormalities in MIS-C to healthy children and those with inflammatory disease reveals distinct inflammatory cytokine production and a monofunctional T cell response.

    Butters, Claire / Benede, Ntombi / Moyo-Gwete, Thandeka / Richardson, Simone I / Rohlwink, Ursula / Shey, Muki / Ayres, Frances / Manamela, Nelia P / Makhado, Zanele / Balla, Sashkia R / Madzivhandila, Mashudu / Ngomti, Amkele / Baguma, Richard / Facey-Thomas, Heidi / Spracklen, Timothy F / Day, Jonathan / van der Ross, Hamza / Riou, Catherine / Burgers, Wendy A /
    Scott, Christiaan / Zühlke, Liesl / Moore, Penny L / Keeton, Roanne S / Webb, Kate

    Clinical immunology (Orlando, Fla.)

    2023  Volume 259, Page(s) 109877

    Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a severe, hyperinflammatory disease that occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune pathology of MIS-C is incompletely understood, ... ...

    Abstract Multisystem inflammatory syndrome in children (MIS-C) is a severe, hyperinflammatory disease that occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying immune pathology of MIS-C is incompletely understood, with limited data comparing MIS-C to clinically similar paediatric febrile diseases at presentation. SARS-CoV-2-specific T cell responses have not been compared in these groups to assess whether there is a T cell profile unique to MIS-C. In this study, we measured inflammatory cytokine concentration and SARS-CoV-2-specific humoral immunity and T cell responses in children with fever and suspected MIS-C at presentation (n = 83) where MIS-C was ultimately confirmed (n = 58) or another diagnosis was made (n = 25) and healthy children (n = 91). Children with confirmed MIS-C exhibited distinctly elevated serum IL-10, IL-6, and CRP at presentation. No differences were detected in SARS-CoV-2 spike IgG serum concentration, neutralisation capacity, antibody dependant cellular phagocytosis, antibody dependant cellular cytotoxicity or SARS-CoV-2-specific T cell frequency between the groups. Healthy SARS-CoV-2 seropositive children had a higher proportion of polyfunctional SARS-CoV-2-specific CD4+ T cells compared to children with MIS-C and those with other inflammatory or infectious diagnoses, who both presented a largely monofunctional SARS-CoV-2-specific CD4+ T cell profile. Treatment with steroids and/or intravenous immunoglobulins resulted in rapid reduction of inflammatory cytokines but did not affect the SARS-CoV-2-specific IgG or CD4+ T cell responses in MIS-C. In these data, MIS-C had a unique cytokine profile but not a unique SARS-CoV-2 specific humoral or T cell cytokine response.
    MeSH term(s) Humans ; Child ; COVID-19 ; SARS-CoV-2 ; Cytokines ; Immunoglobulin G ; Fever ; Antibodies, Viral ; Connective Tissue Diseases ; Systemic Inflammatory Response Syndrome
    Chemical Substances Cytokines ; Immunoglobulin G ; Antibodies, Viral
    Language English
    Publishing date 2023-12-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2023.109877
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: SARS-CoV-2 Antigens Expressed in Plants Detect Antibody Responses in COVID-19 Patients.

    Makatsa, Mohau S / Tincho, Marius B / Wendoh, Jerome M / Ismail, Sherazaan D / Nesamari, Rofhiwa / Pera, Francisco / de Beer, Scott / David, Anura / Jugwanth, Sarika / Gededzha, Maemu P / Mampeule, Nakampe / Sanne, Ian / Stevens, Wendy / Scott, Lesley / Blackburn, Jonathan / Mayne, Elizabeth S / Keeton, Roanne S / Burgers, Wendy A

    Frontiers in plant science

    2021  Volume 12, Page(s) 589940

    Abstract: ... ...

    Abstract Background
    Language English
    Publishing date 2021-03-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2613694-6
    ISSN 1664-462X
    ISSN 1664-462X
    DOI 10.3389/fpls.2021.589940
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity.

    Benede, Ntombi / Tincho, Marius B / Walters, Avril / Subbiah, Vennesa / Ngomti, Amkele / Baguma, Richard / Butters, Claire / Hahnle, Lina / Mennen, Mathilda / Skelem, Sango / Adriaanse, Marguerite / Facey-Thomas, Heidi / Scott, Christiaan / Day, Jonathan / Spracklen, Timothy F / van Graan, Strauss / Balla, Sashkia R / Moyo-Gwete, Thandeka / Moore, Penny L /
    MacGinty, Rae / Botha, Maresa / Workman, Lesley / Johnson, Marina / Goldblatt, David / Zar, Heather J / Ntusi, Ntobeko A B / Zühlke, Liesl / Webb, Kate / Riou, Catherine / Burgers, Wendy A / Keeton, Roanne S

    iScience

    2023  Volume 27, Issue 1, Page(s) 108728

    Abstract: SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on SARS-CoV-2 antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic ... ...

    Abstract SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on SARS-CoV-2 antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4
    Language English
    Publishing date 2023-12-14
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108728
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

    Riou, Catherine / Bhiman, Jinal N / Ganga, Yashica / Sawry, Shobna / Ayres, Frances / Baguma, Richard / Balla, Sashkia R / Benede, Ntombi / Bernstein, Mallory / Besethi, Asiphe S / Cele, Sandile / Crowther, Carol / Dhar, Mrinmayee / Geyer, Sohair / Gill, Katherine / Grifoni, Alba / Hermanus, Tandile / Kaldine, Haajira / Keeton, Roanne S /
    Kgagudi, Prudence / Khan, Khadija / Lazarus, Erica / Le Roux, Jean / Lustig, Gila / Madzivhandila, Mashudu / Magugu, Siyabulela F J / Makhado, Zanele / Manamela, Nelia P / Mkhize, Qiniso / Mosala, Paballo / Motlou, Thopisang P / Mutavhatsindi, Hygon / Mzindle, Nonkululeko B / Nana, Anusha / Nesamari, Rofhiwa / Ngomti, Amkele / Nkayi, Anathi A / Nkosi, Thandeka P / Omondi, Millicent A / Panchia, Ravindre / Patel, Faeezah / Sette, Alessandro / Singh, Upasna / van Graan, Strauss / Venter, Elizabeth M / Walters, Avril / Moyo-Gwete, Thandeka / Richardson, Simone I / Garrett, Nigel / Rees, Helen / Bekker, Linda-Gail / Gray, Glenda / Burgers, Wendy A / Sigal, Alex / Moore, Penny L / Fairlie, Lee

    PLOS global public health

    2024  Volume 4, Issue 4, Page(s) e0002703

    Abstract: We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 ... ...

    Abstract We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article
    ISSN 2767-3375
    ISSN (online) 2767-3375
    DOI 10.1371/journal.pgph.0002703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Distinct T cell functional profiles in SARS-CoV-2 seropositive and seronegative children associated with endemic human coronavirus cross-reactivity

    Benede, Ntombi S. B. / Tincho, Marius B. / Walters, Avril / Subbiah, Vennesa / Ngomti, Amkele / Baguma, Richard / Butters, Claire / Mennen, Mathilda / Skelem, Sango / Adriaanse, Marguerite / van Graan, Strauss / Balla, Sashkia R. / Moyo-Gwete, Thandeka / Moore, Penny L. / Botha, Maresa / Workman, Lesley / Zar, Heather J. / Ntusi, Ntobeko A. B. / Zühlke, Liesl /
    Webb, Kate / Riou, Catherine / Burgers, Wendy A. / Keeton, Roanne S.

    medRxiv

    Abstract: SUMMARY SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic ... ...

    Abstract SUMMARY SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children. Key words: SARS-CoV-2, Children, IgG responses, T cell response, Polyfunctional profile, endemic HCoV
    Keywords covid19
    Language English
    Publishing date 2023-05-23
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.05.16.23290059
    Database COVID19

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  9. Article ; Online: Post-pandemic memory T-cell response to SARS-CoV-2 is durable, broadly targeted and cross-reactive to hypermutated BA.2.86

    Nesamari, Rofhiwa / Omondi, Millicent A / Hoft, Maxine A / Ngomti, Amkele / Baguma, Richard / Nkayi, Anathi A / Besethi, Asiphe S / Magugu, Siyabulela FJ / Mosala, Paballo / Walters, Avril / Clark, Gesina M / Mennen, Mathilda / Skelem, Sango / Adriaanse, Marguerite / Grifoni, Alba / Sette, Alessandro / Keeton, Roanne S / Ntusi, Ntobeko AB / Riou, Catherine /
    Burgers, Wendy A

    medRxiv

    Abstract: The COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has ... ...

    Abstract The COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T-cell immune memory is critical for continued protection against severe COVID-19. We examined T-cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T-cell memory responses in healthcare workers in South Africa (n=39), most of whom had received 2 doses of Ad26.CoV2.S (Johnson & Johnson/Janssen) vaccine and experienced at least one SARS-CoV-2 infection. Spike-specific T cells were highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant non-spike (nucleocapsid and membrane)-specific T cells were detectable in most participants, augmenting the total T-cell resources available for protection. The bulk of SARS-CoV-2-specific T-cell responses had an early-differentiated phenotype, explaining their persistent nature. Thus, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants. Long-term T-cell immune memory is likely to provide continued protection against severe outcomes of COVID-19.
    Keywords covid19
    Language English
    Publishing date 2023-10-30
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.10.28.23297714
    Database COVID19

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  10. Article: Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

    Riou, Catherine / Bhiman, Jinal N / Ganga, Yashica / Sawry, Shobna / Ayres, Frances / Baguma, Richard / Balla, Sashkia R / Benede, Ntombi / Bernstein, Mallory / Besethi, Asiphe S / Cele, Sandile / Crowther, Carol / Dhar, Mrinmayee / Geyer, Sohair / Gill, Katherine / Grifoni, Alba / Hermanus, Tandile / Kaldine, Haajira / Keeton, Roanne S /
    Kgagudi, Prudence / Khan, Khadija / Lazarus, Erica / Roux, Jean Le / Lustig, Gila / Madzivhandila, Mashudu / Magugu, Siyabulela Fj / Makhado, Zanele / Manamela, Nelia P / Mkhize, Qiniso / Mosala, Paballo / Motlou, Thopisang P / Mutavhatsindi, Hygon / Mzindle, Nonkululeko B / Nana, Anusha / Nesamari, Rofhiwa / Ngomti, Amkele / Nkayi, Anathi A / Nkosi, Thandeka P / Omondi, Millicent A / Panchia, Ravindre / Patel, Faeezah / Sette, Alessandro / Singh, Upasna / van Graan, Strauss / Venter, Elizabeth M / Walters, Avril / Moyo-Gwete, Thandeka / Richardson, Simone I / Garrett, Nigel / Rees, Helen / Bekker, Linda-Gail / Gray, Glenda / Burgers, Wendy A / Sigal, Alex / Moore, Penny L / Fairlie, Lee

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Background: We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS- ...

    Abstract Background: We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection.
    Methods: A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated.
    Results: No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting.
    Conclusion: In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost.
    Trial registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841.
    Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH).
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.20.23298785
    Database MEDical Literature Analysis and Retrieval System OnLINE

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