Sheward Lab
The development of effective vaccines against HIV and other highly variable viruses for which there are no licensed vaccines is a major global health priority. The ability to pre-emptively vaccinate against clades of viruses with pandemic potential could also prevent another global pandemic.
Research focus
Next-generation mRNA vaccines
Using state-of-the-art mRNA delivery, we are developing and characterizing next-generation vaccines aiming to elicit broadly neutralizing antibodies that could protect against highly variable viruses or prevent the next pandemic. A current research focus is on the antibody response to vaccine ‘cocktails’.
Adapting the mechanisms and pathways used by viruses to manipulate host cell biology
Viruses are experts at the manipulation of host cells. By characterizing how viruses modify host cell biology we aim to identify mechanisms and pathways that can be exploited to improve mRNA vaccines, or treat other human diseases. A current research focus is on how viruses enhance the translation of their own mRNA, and the adaptation and refinement of these mechanisms to improve mRNA delivery.
Monitor the immune response to infection and vaccination
Using virus neutralization assays we characterize the antibody response following infection and vaccination – using this to inform both vaccine design and public health policy. Over the course of the COVID-19 pandemic we have been monitoring the neutralizing antibody response to SARS-CoV-2 variants at the population level in Sweden.
Selected publications
Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster in Sweden.
Marking U, Bladh O, Aguilera K, Yang Y, Greilert Norin N, Blom K, Hober S, Klingström J, Havervall S, Åberg M, Sheward DJ, Thålin C
Lancet Infect Dis 2024 Feb;24(2):e80-e81
SARS-CoV-2 evolution in the Omicron era.
Roemer C, Sheward DJ, Hisner R, Gueli F, Sakaguchi H, Frohberg N, Schoenmakers J, Sato K, O'Toole Á, Rambaut A, Pybus OG, Ruis C, Murrell B, Peacock TP
Nat Microbiol 2023 Nov;8(11):1952-1959
Sensitivity of the SARS-CoV-2 BA.2.86 variant to prevailing neutralising antibody responses.
Sheward DJ, Yang Y, Westerberg M, Öling S, Muschiol S, Sato K, Peacock TP, Karlsson Hedestam GB, Albert J, Murrell B
Lancet Infect Dis 2023 Nov;23(11):e462-e463
Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.
Pushparaj P, Nicoletto A, Sheward DJ, Das H, Castro Dopico X, Perez Vidakovics L, Hanke L, Chernyshev M, Narang S, Kim S, Fischbach J, Ekström S, McInerney G, Hällberg BM, Murrell B, Corcoran M, Karlsson Hedestam GB
Immunity 2023 Jan;56(1):193-206.e7
Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies.
Sheward DJ, Kim C, Fischbach J, Sato K, Muschiol S, Ehling RA, Björkström NK, Karlsson Hedestam GB, Reddy ST, Albert J, Peacock TP, Murrell B
Lancet Infect Dis 2022 Nov;22(11):1538-1540
Evasion of neutralising antibodies by omicron sublineage BA.2.75.
Sheward DJ, Kim C, Fischbach J, Muschiol S, Ehling RA, Björkström NK, Karlsson Hedestam GB, Reddy ST, Albert J, Peacock TP, Murrell B
Lancet Infect Dis 2022 Oct;22(10):1421-1422
HIV Coinfection Provides Insights for the Design of Vaccine Cocktails to Elicit Broadly Neutralizing Antibodies.
Sheward DJ, Hermanus T, Murrell B, Garrett N, Abdool Karim SS, Morris L, Moore PL, Williamson C
J Virol 2022 Jul;96(14):e0032422
Neutralisation sensitivity of the SARS-CoV-2 omicron (B.1.1.529) variant: a cross-sectional study.
Sheward DJ, Kim C, Ehling RA, Pankow A, Castro Dopico X, Dyrdak R, Martin DP, Reddy ST, Dillner J, Karlsson Hedestam GB, Albert J, Murrell B
Lancet Infect Dis 2022 Jun;22(6):813-820
Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models.
Sheward DJ, Mandolesi M, Urgard E, Kim C, Hanke L, Perez Vidakovics L, Pankow A, Smith NL, Castro Dopico X, McInerney GM, Coquet JM, Karlsson Hedestam GB, Murrell B
Cell Rep Med 2021 Nov;2(11):100450
HIV Superinfection Drives De Novo Antibody Responses and Not Neutralization Breadth.
Sheward DJ, Marais J, Bekker V, Murrell B, Eren K, Bhiman JN, Nonyane M, Garrett N, Woodman ZL, Abdool Karim Q, Abdool Karim SS, Morris L, Moore PL, Williamson C
Cell Host Microbe 2018 Oct;24(4):593-599.e3
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
Doria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, DeKosky BJ, Ernandes MJ, Georgiev IS, Kim HJ, Pancera M, Staupe RP, Altae-Tran HR, Bailer RT, Crooks ET, Cupo A, Druz A, Garrett NJ, Hoi KH, Kong R, Louder MK, Longo NS, McKee K, Nonyane M, O'Dell S, Roark RS, Rudicell RS, Schmidt SD, Sheward DJ, Soto C, Wibmer CK, Yang Y, Zhang Z, , Mullikin JC, Binley JM, Sanders RW, Wilson IA, Moore JP, Ward AB, Georgiou G, Williamson C, Abdool Karim SS, Morris L, Kwong PD, Shapiro L, Mascola JR
Nature 2014 May;509(7498):55-62
Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape.
Moore PL, Gray ES, Wibmer CK, Bhiman JN, Nonyane M, Sheward DJ, Hermanus T, Bajimaya S, Tumba NL, Abrahams MR, Lambson BE, Ranchobe N, Ping L, Ngandu N, Abdool Karim Q, Abdool Karim SS, Swanstrom RI, Seaman MS, Williamson C, Morris L
Nat Med 2012 Nov;18(11):1688-92