We are pleased to announce the 2021 ISV Papers of the Year.
Papers were nominated and selected by the ISV Fellows and Board. In recognition of the continued impact of the COVID-19 pandemic on vaccine development, nominations were collected for best COVID-19 vaccine papers independently of publications about non-COVID vaccines.
Votes were cast for one COVID-19 and one non-COVID-19 paper. The paper with the most votes in its category was selected paper of the year.
Non-COVID 2021 ISV PAPER of the YEAR:
Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma.
Hu Z, Leet DE, Allesøe RL, Oliveira G, Li S, Luoma AM, Liu J, Forman J, Huang T, Iorgulescu JB, Holden R, Sarkizova S, Gohil SH, Redd RA, Sun J, Elagina L, Giobbie-Hurder A, Zhang W, Peter L, Ciantra Z, Rodig S, Olive O, Shetty K, Pyrdol J, Uduman M, Lee PC, Bachireddy P, Buchbinder EI, Yoon CH, Neuberg D, Pentelute BL, Hacohen N, Livak KJ, Shukla SA, Olsen LR, Barouch DH, Wucherpfennig KW, Fritsch EF, Keskin DB, Wu CJ, Ott PA.
Nat Med. 2021 Mar;27(3):515-525. doi: 10.1038/s41591-020-01206-4. Epub 2021 Jan 21. PMID: 33479501; PMCID: PMC8273876.
Personal neoantigen vaccines have been envisioned as an effective approach to induce, amplify and diversify antitumor T cell responses. To define the long-term effects of such a vaccine, we evaluated the clinical outcome and circulating immune responses of eight patients with surgically resected stage IIIB/C or IVM1a/b melanoma, at a median of almost 4 years after treatment with NeoVax, a long-peptide vaccine targeting up to 20 personal neoantigens per patient (NCT01970358). All patients were alive and six were without evidence of active disease. We observed long-term persistence of neoantigen-specific T cell responses following vaccination, with ex vivo detection of neoantigen-specific T cells exhibiting a memory phenotype. We also found diversification of neoantigen-specific T cell clones over time, with emergence of multiple T cell receptor clonotypes exhibiting distinct functional avidities. Furthermore, we detected evidence of tumor infiltration by neoantigen-specific T cell clones after vaccination and epitope spreading, suggesting on-target vaccine-induced tumor cell killing. Personal neoantigen peptide vaccines thus induce T cell responses that persist over years and broaden the spectrum of tumor-specific cytotoxicity in patients with melanoma.
COVID-19 2021 ISV PAPER of the YEAR vote was a tie between:
Evolution of antibody immunity to SARS-CoV-2.
Gaebler C, Wang Z, Lorenzi JCC, Muecksch F, Finkin S, Tokuyama M, Cho A, Jankovic M, Schaefer-Babajew D, Oliveira TY, Cipolla M, Viant C, Barnes CO, Bram Y, Breton G, Hägglöf T, Mendoza P, Hurley A, Turroja M, Gordon K, Millard KG, Ramos V, Schmidt F, Weisblum Y, Jha D, Tankelevich M, Martinez-Delgado G, Yee J, Patel R, Dizon J, Unson-O'Brien C, Shimeliovich I, Robbiani DF, Zhao Z, Gazumyan A, Schwartz RE, Hatziioannou T, Bjorkman PJ, Mehandru S, Bieniasz PD, Caskey M, Nussenzweig MC.
Nature. 2021 Mar;591(7851):639-644. doi: 10.1038/s41586-021-03207-w. Epub 2021 Jan 18. PMID: 33461210; PMCID: PMC8221082.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, Edwards RJ, Gobeil S, Barr M, Mansouri K, Alam SM, Sutherland LL, Cai F, Sanzone AM, Berry M, Manne K, Bock KW, Minai M, Nagata BM, Kapingidza AB, Azoitei M, Tse LV, Scobey TD, Spreng RL, Rountree RW, DeMarco CT, Denny TN, Woods CW, Petzold EW, Tang J, Oguin TH 3rd, Sempowski GD, Gagne M, Douek DC, Tomai MA, Fox CB, Seder R, Wiehe K, Weissman D, Pardi N, Golding H, Khurana S, Acharya P, Andersen H, Lewis MG, Moore IN, Montefiori DC, Baric RS, Haynes BF.
Nature. 2021 Jun;594(7864):553-559. doi: 10.1038/s41586-021-03594-0. Epub 2021 May 10. PMID: 33971664; PMCID: PMC8528238.
Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.