A Phase 1/2A, Randomized Study of a T Follicular Helper (TFH)-Targeting Genetic Vaccine Strategy Designed to Induce Broad, Durable Immune Responses

Summary

The goal of this clinical trial is to test two investigational COVID-19 booster vaccines, called CoTend-s3BXBB and CoTend-BXBB, in healthy volunteers ages 40-64. The CoTend-s3BXBB vaccine includes a component called "s3", which was designed to improve the body's response to the vaccine. CoTend-BXBB is the same vaccine without s3. The main questions the study aims to answer are: 1) Is the investigational vaccine safe? 2) Does "s3" lead to bigger, broader, and longer-lasting responses to the vaccine? 5 different doses of the vaccines will be studied. Participants will receive a single dose of either CoTend-s3BXBB, CoTend-BXBB, or placebo. Participants will be monitored for side effects. Saliva, nasal, and blood samples will be collected and immune responses to the vaccine will be measured.

Timeline

Start

2025-10-21

Primary completion

2027-12

Completion

2029-10

Publications

• Background Bowen JE, Park YJ, Stewart C, Brown JT, Sharkey WK, Walls AC, Joshi A, Sprouse KR, McCallum M, Tortorici MA, Franko NM, Logue JK, Mazzitelli IG, Nguyen AW, Silva RP, Huang Y, Low JS, Jerak J, Tiles SW, Ahmed K, Shariq A, Dan JM, Zhang Z, Weiskopf D, Sette A, Snell G, Posavad CM, Iqbal NT, Geffner J, Bandera A, Gori A, Sallusto F, Maynard JA, Crotty S, Van Voorhis WC, Simmerling C, Grifantini R, Chu HY, Corti D, Veesler D. SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines. Sci Immunol. 2022 Dec 23;7(78):eadf1421. doi: 10.1126/sciimmunol.adf1421. Epub 2022 Dec 23.
• Background De Boer RJ, Perelson AS. How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response. J Virol. 2017 Oct 27;91(22):e00983-17. doi: 10.1128/JVI.00983-17. Print 2017 Nov 15.
• Background Wang Q, Iketani S, Li Z, Liu L, Guo Y, Huang Y, Bowen AD, Liu M, Wang M, Yu J, Valdez R, Lauring AS, Sheng Z, Wang HH, Gordon A, Liu L, Ho DD. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. 2023 Jan 19;186(2):279-286.e8. doi: 10.1016/j.cell.2022.12.018. Epub 2022 Dec 14.
• Background Havervall S, Marking U, Svensson J, Greilert-Norin N, Bacchus P, Nilsson P, Hober S, Gordon M, Blom K, Klingstrom J, Aberg M, Smed-Sorensen A, Thalin C. Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection. N Engl J Med. 2022 Oct 6;387(14):1333-1336. doi: 10.1056/NEJMc2209651. Epub 2022 Sep 14. No abstract available.
• Background Balachandran H, Phetsouphanh C, Agapiou D, Adhikari A, Rodrigo C, Hammoud M, Shrestha LB, Keoshkerian E, Gupta M, Turville S, Christ D, King C, Sasson SC, Bartlett A, Grubor-Bauk B, Rawlinson W, Aggarwal A, Stella AO, Klemm V, Mina MM, Post JJ, Hudson B, Gilroy N, Konecny P, Ahlenstiel G, Dwyer DE, Sorrell TC, Kelleher A, Tedla N, Lloyd AR, Martinello M, Bull RA; COSIN Study Group. Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses. Cell Rep. 2022 Feb 8;38(6):110345. doi: 10.1016/j.celrep.2022.110345. Epub 2022 Jan 19.
• Background Fuchs JD, Bart PA, Frahm N, Morgan C, Gilbert PB, Kochar N, DeRosa SC, Tomaras GD, Wagner TM, Baden LR, Koblin BA, Rouphael NG, Kalams SA, Keefer MC, Goepfert PA, Sobieszczyk ME, Mayer KH, Swann E, Liao HX, Haynes BF, Graham BS, McElrath MJ; NIAID HIV Vaccine Trials Network. Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals. J AIDS Clin Res. 2015 May;6(5):461. doi: 10.4172/2155-6113.1000461. Epub 2015 May 23.
• Background Nwanegbo E, Vardas E, Gao W, Whittle H, Sun H, Rowe D, Robbins PD, Gambotto A. Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States. Clin Diagn Lab Immunol. 2004 Mar;11(2):351-7. doi: 10.1128/cdli.11.2.351-357.2004.
• Background Qu P, Faraone JN, Evans JP, Zheng YM, Yu L, Ma Q, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Durability of Booster mRNA Vaccine against SARS-CoV-2 BA.2.12.1, BA.4, and BA.5 Subvariants. N Engl J Med. 2022 Oct 6;387(14):1329-1331. doi: 10.1056/NEJMc2210546. Epub 2022 Sep 7. No abstract available.
• Background Gilboa M, Regev-Yochay G, Mandelboim M, Indenbaum V, Asraf K, Fluss R, Amit S, Mendelson E, Doolman R, Afek A, Freedman LS, Kreiss Y, Lustig Y. Durability of Immune Response After COVID-19 Booster Vaccination and Association With COVID-19 Omicron Infection. JAMA Netw Open. 2022 Sep 1;5(9):e2231778. doi: 10.1001/jamanetworkopen.2022.31778.
• Background Chen Y, Tong P, Whiteman NB, et al. Differential antibody dynamics to SARS-CoV-2 infection and vaccination. bioRxiv 2021:2021.09.09.459504.
• Background Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM, Planchais C, Porrot F, Robillard N, Puech J, Prot M, Gallais F, Gantner P, Velay A, Le Guen J, Kassis-Chikhani N, Edriss D, Belec L, Seve A, Courtellemont L, Pere H, Hocqueloux L, Fafi-Kremer S, Prazuck T, Mouquet H, Bruel T, Simon-Loriere E, Rey FA, Schwartz O. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021 Aug;596(7871):276-280. doi: 10.1038/s41586-021-03777-9. Epub 2021 Jul 8.

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