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4. Context-restricted PD-(L)1 checkpoint agonism by CTLA4-Ig therapies inhibits T cell activity

Author

Oxley, Ethan P., Kershaw, Nadia J., Louis, Cynthia, Goodall, Katharine J., Garwood, Maximilian M., Jee Ho, Skye Min, Voo, Veronica T.F., Park, Hae-Young, Iaria, Josephine, Wong, Lilian L.L., Lebenbaum, Ariel G., Wiranata, Stephanie, Pang, Ee Shan, Edwards, Emily S.J., D’Silva, Damian B., Hansen, Jacinta, van Zelm, Menno C., O’Keeffe, Meredith, Hogarth, P. Mark, Haynes, Nicole M., Huntington, Nicholas D., Wicks, Ian P., and Dickins, Ross A.

Published
2024
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6. Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants

Author

Fryer, Holly A., Geers, Daryl, Gommers, Lennert, Zaeck, Luca M., Tan, Ngoc H., Jones-Freeman, Bernadette, Goorhuis, Abraham, Postma, Douwe F., Visser, Leo G., Hogarth, P. Mark, Koopmans, Marion P.G., GeurtsvanKessel, Corine H., O’Hehir, Robyn E., van der Kuy, P. Hugo M., de Vries, Rory D., and van Zelm, Menno C.

Published
2024
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8. Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children

Author

Chan, Jo-Anne, Loughland, Jessica R, de la Parte, Lauren, Okano, Satomi, Ssewanyana, Isaac, Nalubega, Mayimuna, Nankya, Felistas, Musinguzi, Kenneth, Rek, John, Arinaitwe, Emmanuel, Tipping, Peta, Bourke, Peter, Andrew, Dean, Dooley, Nicholas, SheelaNair, Arya, Wines, Bruce D, Hogarth, P Mark, Beeson, James G, Greenhouse, Bryan, Dorsey, Grant, Kamya, Moses, Hartel, Gunter, Minigo, Gabriela, Feeney, Margaret, Jagannathan, Prasanna, and Boyle, Michelle J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Prevention, Biotechnology, Vector-Borne Diseases, Malaria, Immunization, Clinical Research, Pediatric, Infectious Diseases, Vaccine Related, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Inflammatory and immune system, Infection, Good Health and Well Being, Adult, Antibodies, Protozoan, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, T Follicular Helper Cells, T-Lymphocytes, Helper-Inducer, Uganda
Abstract

T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.

Published
2022

10. Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants

Author

Haycroft, Ebene R., Davis, Samantha K., Ramanathan, Pradhipa, Lopez, Ester, Purcell, Ruth A., Tan, Li Lynn, Pymm, Phillip, Wines, Bruce D., Hogarth, P. Mark, Wheatley, Adam K., Juno, Jennifer A., Redmond, Samuel J., Gherardin, Nicholas A., Godfrey, Dale I., Tham, Wai-Hong, Selva, Kevin John, Kent, Stephen J., and Chung, Amy W.

Published
2023
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11. Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians

Author

Hensen, Luca, Nguyen, Thi H. O., Rowntree, Louise C., Damelang, Timon, Koutsakos, Marios, Aban, Malet, Hurt, Aeron, Harland, Kim L., Auladell, Maria, van de Sandt, Carolien E., Everitt, Anngie, Blacker, Cath, Oyong, Damian A., Loughland, Jessica R., Webb, Jessica R., Wines, Bruce D., Hogarth, P. Mark, Flanagan, Katie L., Plebanski, Magdalena, Wheatley, Adam, Chung, Amy W., Kent, Stephen J., Miller, Adrian, Clemens, E. Bridie, Doherty, Peter C., Nelson, Jane, Davies, Jane, Tong, Steven Y. C., and Kedzierska, Katherine

Published
2021

12. Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.

Author

Grobben, Marloes, Bakker, Margreet, Schriek, Angela I., Levels, Liesbeth J.J., Umotoy, Jeffrey C., Tejjani, Khadija, van Breemen, Mariëlle J., Lin, Ryan N., de Taeye, Steven W., Ozorowski, Gabriel, Kootstra, Neeltje A., Ward, Andrew B., Kent, Stephen J., Hogarth, P. Mark, Wines, Bruce D., Sanders, Rogier W., Chung, Amy W., and van Gils, Marit J.

Subjects
ANTIBODY formation, IMMUNE response, DISEASE progression, HIV, PROTEIN-protein interactions
Abstract

HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood. To identify a specific profile of antibody features associated with delayed disease progression, we studied antibody polyfunctionality during untreated HIV-1 infection in the well-documented Amsterdam Cohort Studies. Serum samples were analyzed from untreated individuals with HIV-1 at approximately 6 months (n = 166) and 3 years (n = 382) post-seroconversion (post-SC). A Luminex antibody Fc array was used to profile 15 different Fc features for serum antibodies against 20 different HIV-1 envelope glycoprotein antigens and the resulting data was also compared with data on neutralization breadth. We found that high HIV-1 specific IgG1 levels and low IgG2 and IgG4 levels at 3 years post-SC were associated with delayed disease progression. Moreover, delayed disease progression was associated with a broad and polyfunctional antibody response. Specifically, the capacity to interact with all Fc γ receptors (FcγRs) and C1q, and in particular with FcγRIIa, correlated positively with delayed disease progression. There were strong correlations between antibody Fc features and neutralization breadth and several antibody features that were associated with delayed disease progression were also associated with the development of broad and potent antibody neutralization. In summary, we identified a strong association between broad, polyfunctional antibodies and delayed disease progression. These findings contribute new information for the fight against HIV-1, especially for new antibody-based therapy and cure strategies. Author summary: Despite the availability of effective treatment, HIV-1 still causes significant mortality and morbidity across the globe. Alternative ways for protection or treatment against HIV-1 are needed. Antibody-mediated effector functions could potentially contribute to the effectiveness of novel approaches. However, we need more information on which antibody properties are associated with these potential beneficial functions of antibodies. Studying antibody responses during natural HIV-1 infection can provide guidance on this topic. This study identified several antibody properties that were associated with reduced HIV-1 disease progression in a large cohort of individuals with untreated HIV-1. High levels of IgG1 and low levels of IgG2 and IgG4, broad and polyfunctional antibodies and interaction with immune proteins FcyRs and C1q, were all associated with delayed disease progression. Subsequently, effective strategies against HIV-1 will likely require multiple different components, and the antibody properties described in this study may contribute to a more detailed bio-molecular roadmap for antibody-based strategies for HIV-1 prevention, therapy and cure. [ABSTRACT FROM AUTHOR]

Published
2024
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16. A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

Author

Fulford, Thomas S., Van, Huy, Gherardin, Nicholas A., Zheng, Shuning, Ciula, Marcin, Drummer, Heidi E., Redmond, Samuel, Tan, Hyon-Xhi, Boo, Irene, Center, Rob J., Li, Fan, Grimley, Samantha L., Wines, Bruce D., Nguyen, Thi H.O., Mordant, Francesca L., Ellenberg, Paula, Rowntree, Louise C., Kedzierski, Lukasz, Cheng, Allen C., Doolan, Denise L., Matthews, Gail, Bond, Katherine, Hogarth, P. Mark, McQuilten, Zoe, Subbarao, Kanta, Kedzierska, Katherine, Juno, Jennifer A., Wheatley, Adam K., Kent, Stephen J., Williamson, Deborah A., Purcell, Damian F.J., Anderson, David A., and Godfrey, Dale I.

Published
2021
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17. Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial

Author

Chappell, Keith J, Mordant, Francesca L, Li, Zheyi, Wijesundara, Danushka K, Ellenberg, Paula, Lackenby, Julia A, Cheung, Stacey T M, Modhiran, Naphak, Avumegah, Michael S, Henderson, Christina L, Hoger, Kym, Griffin, Paul, Bennet, Jillian, Hensen, Luca, Zhang, Wuji, Nguyen, Thi H O, Marrero-Hernandez, Sara, Selva, Kevin J, Chung, Amy W, Tran, Mai H, Tapley, Peter, Barnes, James, Reading, Patrick C, Nicholson, Suellen, Corby, Stavroula, Holgate, Thomas, Wines, Bruce D, Hogarth, P Mark, Kedzierska, Katherine, Purcell, Damian F J, Ranasinghe, Charani, Subbarao, Kanta, Watterson, Daniel, Young, Paul R, and Munro, Trent P

Published
2021
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20. Stellabody: A novel hexamer‐promoting mutation for improved IgG potency.

Author

Whitehead, Clarissa A., Wines, Bruce D., Davies, Anna M., McDonnell, James M., Trist, Halina M., Esparon, Sandra E., and Hogarth, P. Mark

Subjects
FC receptors, IMMUNOTECHNOLOGY, CYTOTOXINS, IMMUNOGLOBULIN G, MONOCLONAL antibodies
Abstract

Summary: Advances in antibody engineering are being directed at the development of next generation immunotherapeutics with improved potency. Hexamerisation of IgG is a normal physiological aspect of IgG biology and recently described mutations that facilitate this process have a substantial impact upon monoclonal antibody behavior resulting in the elicitation of dramatically enhanced complement‐dependent cytotoxicity, Fc receptor function, and enhanced antigen binding effects, such as targeted receptor agonism or microbe neutralization. Whereas the discovery of IgG hexamerisation enhancing mutations has largely focused on residues with exposure at the surface of the Fc‐Fc and CH2‐CH3 interfaces, our unique approach is the engineering of the mostly buried residue H429 in the CH3 domain. Selective substitution at position 429 forms the basis of Stellabody technology, where the choice of amino acid results in distinct hexamerisation outcomes. H429F results in monomeric IgG that hexamerises after target binding, so called "on‐target" hexamerisation, while the H429Y mutant forms pH‐sensitive hexamers in‐solution prior to antigen binding. Moreover, Stellabody technologies are broadly applicable across the family of antibody‐based biologic therapeutics, including conventional mAbs, bispecific mAbs, and Ig‐like biologics such as Fc‐fusions, with applications in diverse diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections

Author

Selva, Kevin J., primary, Ramanathan, Pradhipa, additional, Haycroft, Ebene R., additional, Reynaldi, Arnold, additional, Cromer, Deborah, additional, Tan, Chee Wah, additional, Wang, Lin-Fa, additional, Wines, Bruce D., additional, Hogarth, P. Mark, additional, Downie, Laura E., additional, Davis, Samantha K., additional, Purcell, Ruth A., additional, Kent, Helen E., additional, Juno, Jennifer A., additional, Wheatley, Adam K., additional, Davenport, Miles P., additional, Kent, Stephen J., additional, and Chung, Amy W., additional

Published
2023
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27. Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after with mRNA but not adenovirus priming

Author

Hartley, Gemma E., primary, Fryer, Holly A., additional, Gill, Paul A., additional, Boo, Irene, additional, Bornheimer, Scott J., additional, Hogarth, P. Mark, additional, Drummer, Heidi E., additional, O'Hehir, Robyn E., additional, Edwards, Emily S.J., additional, and van Zelm, Menno C., additional

Published
2023
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28. Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques

Author

Parsons, Matthew S., Lee, Wen Shi, Kristensen, Anne B., Amarasena, Thakshila, Khoury, Georges, Wheatley, Adam K., Reynaldi, Arnold, Wines, Bruce D., Hogarth, P. Mark, Davenport, Miles P., and Kent, Stephen J.

Subjects
Dosage and administration, Health aspects, Risk factors, Drug therapy, Anti-HIV agents -- Dosage and administration, Macaques -- Health aspects, HIV infections -- Risk factors -- Drug therapy
Abstract

IntroductionPassive administration of broadly neutralizing antibodies (BnAbs) reliably protects nonhuman primates from chimeric simian-human immunodeficiency virus (SHIV) challenge. A range of BnAbs delivered via either i.v. or mucosal routes consistently [...], A considerable body of evidence suggests that Fc-dependent functions improve the capacity of broadly neutralizing antibodies (BnAbs) to protect against and control HIV-1 infection. This phenomenon, however, has not been formally tested in robust cell-associated macaque simian-human immunodeficiency virus (SHIV) models with newer-generation BnAbs. We studied both the WT BnAb PGT121 and a LALA mutant of PGT121 (which has impaired Fc-dependent functions) for their ability to protect pigtail macaques from an i.v. high-dose cell-associated [SHIV.sub.SF162P3] challenge. We found that both WT and LALA PGT121 completely protected all 12 macaques studied. Further, partial depletion of NK cells, key mediators of Fc-dependent functions, did not abrogate the protective efficacy of PGT121 in 6 macaques. Additionally, in animals with established [SHIV.sub.SF162P3] infection, SHIV viremia levels were equally rapidly reduced by LALA and WT PGT121. Our studies suggest that the potent neutralizing capacity of PGT121 renders the Fc-dependent functions of the Ab at least partially redundant. These findings have implications for Ab-mediated protection from and control of HIV-1 infection.

Published
2019
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32. Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations

Author

Habel, Jennifer R., primary, Chua, Brendon Y., additional, Kedzierski, Lukasz, additional, Selva, Kevin J., additional, Damelang, Timon, additional, Haycroft, Ebene R., additional, Nguyen, Thi H.O., additional, Koay, Hui-Fern, additional, Nicholson, Suellen, additional, McQuilten, Hayley A., additional, Jia, Xiaoxiao, additional, Allen, Lilith F., additional, Hensen, Luca, additional, Zhang, Wuji, additional, van de Sandt, Carolien E., additional, Neil, Jessica A., additional, Pragastis, Katherine, additional, Lau, Jillian S.Y., additional, Jumarang, Jaycee, additional, Allen, E. Kaitlynn, additional, Amanant, Fatima, additional, Krammer, Florian, additional, Wragg, Kathleen M., additional, Juno, Jennifer A., additional, Wheatley, Adam K., additional, Tan, Hyon-Xhi, additional, Pell, Gabrielle, additional, Walker, Susan, additional, Audsley, Jennifer, additional, Reynaldi, Arnold, additional, Thevarajan, Irani, additional, Denholm, Justin T., additional, Subbarao, Kanta, additional, Davenport, Miles P., additional, Hogarth, P. Mark, additional, Godfrey, Dale I., additional, Cheng, Allen C., additional, Tong, Steven Y.C., additional, Bond, Katherine, additional, Williamson, Deborah A., additional, McMahon, James H., additional, Thomas, Paul G., additional, Pannaraj, Pia S., additional, James, Fiona, additional, Holmes, Natasha E., additional, Smibert, Olivia C., additional, Trubiano, Jason A., additional, Gordon, Claire L., additional, Chung, Amy W., additional, Whitehead, Clare L., additional, Kent, Stephen J., additional, Lappas, Martha, additional, Rowntree, Louise C., additional, and Kedzierska, Katherine, additional

Published
2023
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34. COVID-19 adenoviral vector vaccination elicits a robust memory B cell response with the capacity to recognize Omicron BA.2 and BA.5 variants

Author

Fryer, Holly A., primary, Hartley, Gemma E., additional, Edwards, Emily S.J., additional, Varese, Nirupama, additional, Boo, Irene, additional, Bornheimer, Scott J., additional, Hogarth, P. Mark, additional, Drummer, Heidi E., additional, O’Hehir, Robyn E., additional, and van Zelm, Menno C., additional

Published
2023
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35. The FcγR of Humans and Non-human Primates and Their Interaction with IgG: Implications for Induction of Inflammation, Resistance to Infection and the Use of Therapeutic Monoclonal Antibodies

Author

Hogarth, P. Mark, Anania, Jessica C., Wines, Bruce D., Compans, Richard W, Series editor, Cooper, Max D., Series editor, Gleba, Yuri Y., Series editor, Honjo, Tasuku, Series editor, Oldstone, Michael B. A., Series editor, Vogt, Peter K., Series editor, Malissen, Bernard, Series editor, Aktories, Klaus, Series editor, Kawaoka, Yoshihiro, Series editor, Rappuoli, Rino, Series editor, Galan, Jorge E., Series editor, Ahmed, Rafi, Series editor, Daeron, Marc, editor, and Nimmerjahn, Falk, editor

Published
2014
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36. Corrigendum: Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

Author

Wines, Bruce D., Kurtovic, Liriye, Trist, Halina M., Esparon, Sandra, Lopez, Ester, Chappin, Klasina, Chan, Li-Jin, Mordant, Francesca L., Lee, Wen Shi, Gherardin, Nicholas A., Patel, Sheila K., Hartley, Gemma E., Pymm, Phillip, Cooney, James P., Beeson, James G., Godfrey, Dale I., Burrell, Louise M., van Zelm, Menno C., Wheatley, Adam K., Chung, Amy W., Tham, Wai-Hong, Subbarao, Kanta, Kent, Stephen J., and Hogarth, P. Mark

Subjects
Immunology, Immunology and Allergy
Published
2023
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39. Fc Receptors

Author

Powell, Maree S., Hogarth, P. Mark, Back, Nathan, editor, Cohen, Irun R., editor, Lajtha, Abel, editor, Lambris, John D., editor, Paoletti, Rodolfo, editor, and Sigalov, Alexander B., editor

Published
2008
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40. Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques

Author

Chua, Brendon Y., primary, Sekiya, Toshiki, additional, Koutsakos, Marios, additional, Nomura, Naoki, additional, Rowntree, Louise C., additional, Nguyen, Thi H. O., additional, McQuilten, Hayley A., additional, Ohno, Marumi, additional, Ohara, Yuki, additional, Nishimura, Tomohiro, additional, Endo, Masafumi, additional, Itoh, Yasushi, additional, Habel, Jennifer R., additional, Selva, Kevin J., additional, Wheatley, Adam K., additional, Wines, Bruce D., additional, Hogarth, P. Mark, additional, Kent, Stephen J., additional, Chung, Amy W., additional, Jackson, David C., additional, Brown, Lorena E., additional, Shingai, Masashi, additional, Kedzierska, Katherine, additional, and Kida, Hiroshi, additional

Published
2022
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41. RNA sequencing of single allergen‐specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect

Author

McKenzie, Craig I., primary, Varese, Nirupama, additional, Aui, Pei Mun, additional, Reinwald, Simone, additional, Wines, Bruce D., additional, Hogarth, P. Mark, additional, Thien, Francis, additional, Hew, Mark, additional, Rolland, Jennifer M., additional, O'Hehir, Robyn E., additional, and van Zelm, Menno C., additional

Published
2022
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45. Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

Author

Wines, Bruce D., primary, Kurtovic, Liriye, additional, Trist, Halina M., additional, Esparon, Sandra, additional, Lopez, Ester, additional, Chappin, Klasina, additional, Chan, Li-Jin, additional, Mordant, Francesca L., additional, Lee, Wen Shi, additional, Gherardin, Nicholas A., additional, Patel, Sheila K., additional, Hartley, Gemma E., additional, Pymm, Phillip, additional, Cooney, James P., additional, Beeson, James G., additional, Godfrey, Dale I., additional, Burrell, Louise M., additional, van Zelm, Menno C., additional, Wheatley, Adam K., additional, Chung, Amy W., additional, Tham, Wai-Hong, additional, Subbarao, Kanta, additional, Kent, Stephen J., additional, and Hogarth, P. Mark, additional

Published
2022
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46. Altered affinity to ACE2 and reduced Fc functional antibodies to SARS-CoV-2 RBD variants

Author

Haycroft, Ebene R, primary, Davis, Samantha K, additional, Ramanathan, Pradhipa, additional, Lopez, Ester, additional, Purcell, Ruth A, additional, Tan, Li Lynn, additional, Pymm, Phillip, additional, Wines, Bruce D, additional, Hogarth, P Mark, additional, Wheatley, Adam K, additional, Juno, Jennifer A., additional, Redmond, Samuel, additional, Gheradin, Nicholas A, additional, Godfrey, Dale I, additional, Tham, Wai-Hong, additional, Selva, Kevin John, additional, Kent, Stephen J, additional, and Chung, Amy W, additional

Published
2022
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48. Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques

Author

Chua, Brendon Y., Sekiya, Toshiki, Koutsakos, Marios, Nomura, Naoki, Rowntree, Louise C., Nguyen, Thi H. O., McQuilten, Hayley A., 1000050794202, Ohno, Marumi, Ohara, Yuki, Nishimura, Tomohiro, Endo, Masafumi, Itoh, Yasushi, Habel, Jennifer R., Selva, Kevin J., Wheatley, Adam K., Wines, Bruce D., Hogarth, P. Mark, Kent, Stephen J., Chung, Amy W., Jackson, David C., Brown, Lorena E., 1000080421981, Shingai, Masashi, Kedzierska, Katherine, 1000010109506, Kida, Hiroshi, Chua, Brendon Y., Sekiya, Toshiki, Koutsakos, Marios, Nomura, Naoki, Rowntree, Louise C., Nguyen, Thi H. O., McQuilten, Hayley A., 1000050794202, Ohno, Marumi, Ohara, Yuki, Nishimura, Tomohiro, Endo, Masafumi, Itoh, Yasushi, Habel, Jennifer R., Selva, Kevin J., Wheatley, Adam K., Wines, Bruce D., Hogarth, P. Mark, Kent, Stephen J., Chung, Amy W., Jackson, David C., Brown, Lorena E., 1000080421981, Shingai, Masashi, Kedzierska, Katherine, 1000010109506, and Kida, Hiroshi

Abstract

Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their efficacy can be modest, especially in immunologically-naive individuals. We investigated immune responses towards inactivated whole influenza virus particle vaccine (WPV) formulations, predicated to be more immunogenic, in a non-human primate model, as an important step towards clinical testing in humans. Comprehensive analyses were used to capture 46 immune parameters to profile how WPV-induced responses differed to those elicited by antigenically-similar SV formulations. Naive cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV consistently induced stronger antibody responses and hemagglutination inhibition (HI) antibody titres against vaccine-matched viruses compared to SV formulations, while acute reactogenic effects were similar. Responses in WPV-primed animals were further increased by boosting with the same formulation, conversely to modest responses after priming and boosting with SV. 28-parameter multiplex bead array defined key antibody features and showed that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV increased IgG responses against A/H1N1 hemagglutinin (HA) and HA-Stem, and higher IgA responses to A/H1N1-HA after each vaccine dose. Antibodies to A/H1N1-HA and HA-Stem that could engage Fc gamma R2a and Fc gamma R3a were also present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. Furthermore, WPV-enhanced antibody responses were associated with higher frequencies of HA-specific B-cells and IFN-gamma-producing CD4(+) T-cell responses. Our data additionally demonstrate stronger boosting of HI titres by WPV following prior infection and support WPV administered as a priming dose irrespective of the follow up vaccine for the second dose. Our findings thus show that compared to SV vaccination, WPV-induced humoral re

Published
2022

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