A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients

Zhe Zhang; Wenjing Yang; Zhengshan Chen; Haoang Chi; Shipo Wu; Wanru Zheng; Ruochun Jin; Busen Wang; Yudong Wang; Nan Huo; Jinlong Zhang; Xiaohong Song; Liyang Xu; Jun Zhang; Lihua Hou; Wei Chen

doi:10.1016/j.xinn.2024.100603

The Innovation > 2024 Vol. 5 > No. 3

Next Article Previous Article

ARTICLE Open Access

Cite PDF

A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients

1.
Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China
2.
Department of Intelligent Data Science, College of Computer Science and Technology, National University of Defense Technology, Changsha 410073, China
3.
Intelligent Game and Decision Lab, Academy of Military Science, Beijing 100091, China

More Information

⁴ These authors contributed equally
Corresponding authors: houlihua@sina.com (L.H.); cw0226@foxmail.com (W.C.)
Received Date: July 07, 2023

Accepted Date: February 28, 2024

Published Online: March 02, 2024

The Innovation 5(3), https://doi.org/10.1016/j.xinn.2024.100603 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

DownLoad: Full size image

PUBLIC SUMMARY

PUBLIC SUMMARY
1. ■ The increase in GP_1,2-specific IgG induced by Ad5-EBOV was strongly correlated with the development of early antiviral and inflammatory responses.
2. ■ Greater innate immune responses were elicited in Ad5-EBOV recipients with lower preexisting Ad5 immunity.
3. ■ A general causality-based tool was proposed to analyze multiomics vaccine immune responses.

ABSTRACT

ABSTRACT

The vaccine-induced innate immune response is essential for the generation of an antibody response. To date, how Ad5-vectored vaccines are influenced by preexisting anti-Ad5 antibodies during activation of the early immune response remains unclear. Here, we investigated the specific alterations in GP_1,2-specific IgG-related elements of the early immune response at the genetic, molecular, and cellular levels on days 0, 1, 3, and 7 after Ad5-EBOV vaccination. In a causal multiomics analysis, distinct early immune responses associated with GP_1,2-specific IgG were observed in Ad5-EBOV recipients with a low level of preexisting anti-Ad5 antibodies. This study revealed the correlates of the Ad5-EBOV-induced IgG response and provided mechanistic evidence for overcoming preexisting Ad5 immunity during the administration of Ad5-vectored vaccines.

FullText(HTML)

REFERENCES

[1]	Tatsis, N., and Ertl, H.C.J. (2004). Adenoviruses as vaccine vectors. Mol. Ther. 10(4): 616–629. https://doi.org/10.1016/j.ymthe.2004.07.013. View in Article CrossRef Google Scholar
[2]	Chang, J. (2021). Adenovirus Vectors: Excellent Tools for Vaccine Development. Immune Netw. 21(1): e6. https://doi.org/10.4110/in.2021.21.e6. View in Article CrossRef Google Scholar
[3]	Cheng, C., Gall, J.G.D., Kong, W.P., et al. (2007). Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells. PLoS Pathog. 3(2): e25. https://doi.org/10.1371/journal.ppat.0030025. View in Article CrossRef Google Scholar
[4]	Zhu, F.C., Wurie, A.H., Hou, L.H., et al. (2017). Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a singlecentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 389(10069): 621–628. https://doi.org/10.1016/s0140-6736(16)32617-4. View in Article CrossRef Google Scholar
[5]	Dolzhikova, I.V., Zubkova, O.V., Tukhvatulin, A.I., et al. (2017). Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia. Hum. Vaccines Immunother. 13(3): 613–620. https://doi.org/10.1080/21645515.2016.1238535. View in Article CrossRef Google Scholar
[6]	Guo, Q., Chan, J.F.W., Poon, V.K.M., et al. (2018). Immunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models. J. Infect. Dis. 218(3): 365–377. https://doi.org/10.1093/infdis/jiy187. View in Article CrossRef Google Scholar
[7]	Baden, L.R., Stieh, D.J., Sarnecki, M., et al. (2020). Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study. Lancet. HIV 7(10): e688–e698. https://doi.org/10.1016/s2352-3018(20)30229-0. View in Article CrossRef Google Scholar
[8]	Jacob-Dolan, C., and Barouch, D.H. (2022). COVID-19 Vaccines: Adenoviral Vectors. Annu. Rev. Med. 73: 41–54. https://doi.org/10.1146/annurev-med-012621-102252. View in Article CrossRef Google Scholar
[9]	Zhu, F.C., Hou, L.H., Li, J.X., et al. (2015). Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet 385(9984): 2272–2279. https://doi.org/10.1016/s0140-6736(15)60553-0. View in Article CrossRef Google Scholar
[10]	Zhu, F.C., Li, Y.H., Guan, X.H., et al. (2020). Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet 395(10240): 1845–1854. https://doi.org/10.1016/s0140-6736(20)31208-3. View in Article CrossRef Google Scholar
[11]	Malik, S., Kishore, S., Nag, S., et al. (2023). Ebola Virus Disease Vaccines: Development, Current Perspectives & Challenges. Vaccines 11(2): 268. https://doi.org/10.3390/vaccines11020268. View in Article CrossRef Google Scholar
[12]	Fausther-Bovendo, H., and Kobinger, G.P. (2014). Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what’s important? Hum. Vaccines Immunother. 10(10): 2875–2884. https://doi.org/10.4161/hv.29594. View in Article CrossRef Google Scholar
[13]	Seregin, S.S., and Amalfitano, A. (2009). Overcoming pre-existing adenovirus immunity by genetic engineering of adenovirus-based vectors. Expet Opin. Biol. Ther. 9(12): 1521–1531. https://doi.org/10.1517/14712590903307388. View in Article CrossRef Google Scholar
[14]	Roberts, D.M., Nanda, A., Havenga, M.J.E., et al. (2006). Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. Nature 441(7090): 239–243. https://doi.org/10.1038/nature04721. View in Article CrossRef Google Scholar
[15]	Croyle, M.A., Patel, A., Tran, K.N., et al. (2008). Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice. PLoS One 3(10): e3548. https://doi.org/10.1371/journal.pone.0003548. View in Article CrossRef Google Scholar
[16]	Barouch, D.H., Pau, M.G., Custers, J.H.H.V., et al. (2004). Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. J. Immunol. 172(10): 6290–6297. https://doi.org/10.4049/jimmunol.172.10.6290. View in Article CrossRef Google Scholar
[17]	Iwasaki, A., and Medzhitov, R. (2015). Control of adaptive immunity by the innate immune system. Nat. Immunol. 16(4): 343–353. https://doi.org/10.1038/ni.3123. View in Article CrossRef Google Scholar
[18]	Rhee, E.G., Blattman, J.N., Kasturi, S.P., et al. (2011). Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors. J. Virol. 85(1): 315–323. https://doi.org/10.1128/jvi.01597-10. View in Article CrossRef Google Scholar
[19]	Collignon, C., Bol, V., Chalon, A., et al. (2020). Innate Immune Responses to Chimpanzee Adenovirus Vector 155 Vaccination in Mice and Monkeys. Front. Immunol. 11: 579872. https://doi.org/10.3389/fimmu.2020.579872. View in Article CrossRef Google Scholar
[20]	Ye, Y., Zhang, Y., Yang, N., et al. (2022). Profiling of immune features to predict immunotherapy efficacy. Innovation 3(1): 100194. https://doi.org/10.1016/j.xinn.2021.100194. View in Article CrossRef Google Scholar
[21]	Provine, N.M., Amini, A., Garner, L.C., et al. (2021). MAIT cell activation augments adenovirus vector vaccine immunogenicity. Science 371(6528): 521–526. https://doi.org/10.1126/science.aax8819. View in Article CrossRef Google Scholar
[22]	Shen, C.F., Yen, C.L., Fu, Y.C., et al. (2022). Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination. Front. Immunol. 13: 807454. https://doi.org/10.3389/fimmu.2022.807454. View in Article CrossRef Google Scholar
[23]	Raeven, R.H.M., van Riet, E., Meiring, H.D., et al. (2019). Systems vaccinology and big data in the vaccine development chain. Immunology 156(1): 33–46. https://doi.org/10.1111/imm.13012. View in Article CrossRef Google Scholar
[24]	Rappuoli, R., Siena, E., and Finco, O. (2018). Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? Systems Biology Views of Vaccine Innate and Adaptive Immunity. Cold Spring Harbor Perspect. Biol. 10(8): a029256. https://doi.org/10.1101/cshperspect.a029256. View in Article CrossRef Google Scholar
[25]	Kazmin, D., Nakaya, H.I., Lee, E.K., et al. (2017). Systems analysis of protective immune responses to RTS, S malaria vaccination in humans. Proc. Natl. Acad. Sci. USA 114(9): 2425–2430. https://doi.org/10.1073/pnas.1621489114. View in Article CrossRef Google Scholar
[26]	Pinski, A.N., and Messaoudi, I. (2020). To B or Not to B: Mechanisms of Protection Conferred by rVSV-EBOV-GP and the Roles of Innate and Adaptive Immunity. Microorganisms 8(10): 1473. https://doi.org/10.3390/microorganisms8101473. View in Article CrossRef Google Scholar
[27]	Arunachalam, P.S., Scott, M.K.D., Hagan, T., et al. (2021). Systems vaccinology of the BNT162b2 mRNA vaccine in humans. Nature 596(7872): 410–416. https://doi.org/10.1038/s41586-021-03791-x. View in Article CrossRef Google Scholar
[28]	Pinschewer, D.D. (2017). Virally vectored vaccine delivery: medical needs, mechanisms, advantages and challenges. Swiss Med. Wkly. 147: w14465. https://doi.org/10.4414/smw.2017.14465. View in Article CrossRef Google Scholar
[29]	Bottermann, M., Foss, S., van Tienen, L.M., et al. (2018). TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination. Proc. Natl. Acad. Sci. USA 115(41): 10440–10445. https://doi.org/10.1073/pnas.1806314115. View in Article CrossRef Google Scholar
[30]	Zak, D.E., Andersen-Nissen, E., Peterson, E.R., et al. (2012). Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity. Proc. Natl. Acad. Sci. USA 109(50): E3503–E3512. https://doi.org/10.1073/pnas.1208972109. View in Article CrossRef Google Scholar
[31]	McElroy, A.K., Erickson, B.R., Flietstra, T.D., et al. (2014). Biomarker correlates of survival in pediatric patients with Ebola virus disease. Emerg. Infect. Dis. 20(10): 1683–1690. https://doi.org/10.3201/eid2010.140430. View in Article CrossRef Google Scholar
[32]	Bergamaschi, C., Terpos, E., Rosati, M., et al. (2021). Systemic IL-15, IFN-g, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients. Cell Rep. 36(6): 109504. https://doi.org/10.1016/j.celrep.2021.109504. View in Article CrossRef Google Scholar
[33]	Tian, Y., Seumois, G., De-Oliveira-Pinto, L.M., et al. (2019). Molecular Signatures of Dengue Virus-Specific IL-10/IFN-g Co-producing CD4 T Cells and Their Association with Dengue Disease. Cell Rep. 29(13): 4482–4495.e4. https://doi.org/10.1016/j.celrep.2019.11.098. View in Article CrossRef Google Scholar
[34]	Huttner, A., Combescure, C., Grillet, S., et al. (2017). A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa. Sci. Transl. Med. 9(385): eaaj1701. https://doi.org/10.1126/scitranslmed.aaj1701. View in Article CrossRef Google Scholar
[35]	Takano, T., Morikawa, M., Adachi, Y., et al. (2022). Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine. Cell Rep. Med. 3(5): 100631. https://doi.org/10.1016/j.xcrm.2022.100631. View in Article CrossRef Google Scholar
[36]	Rechtien, A., Richert, L., Lorenzo, H., et al. (2017). Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV. Cell Rep. 20(9): 2251–2261. https://doi.org/10.1016/j.celrep.2017.08.023. View in Article CrossRef Google Scholar
[37]	Rinchai, D., Deola, S., Zoppoli, G., et al. (2022). High-temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines. Sci. Adv. 8(45): eabp9961. https://doi.org/10.1126/sciadv.abp9961. View in Article CrossRef Google Scholar
[38]	Ryan, F.J., Norton, T.S., McCafferty, C., et al. (2023). A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines. Cell Rep. Med. 4(3): 100971. https://doi.org/10.1016/j.xcrm.2023.100971. View in Article CrossRef Google Scholar
[39]	Huang, M., Zheng, H., Tan, W., et al. (2023). Molecular Signatures in Swine Innate and Adaptive Immune Responses to African Swine Fever Virus Antigens p30/p54/CD2v Expressed Using a Highly Efficient Semliki Forest Virus Replicon System. Int. J. Mol. Sci. 24(11): 9316. https://doi.org/10.3390/ijms24119316. View in Article CrossRef Google Scholar
[40]	Haralambieva, I.H., Oberg, A.L., Dhiman, N., et al. (2012). High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination. J. Infect. Dis. 206(10): 1512–1520. https://doi.org/10.1093/infdis/jis546. View in Article CrossRef Google Scholar
[41]	Sun, Z., Ke, L., Zhao, Q., et al. (2023). The use of bioinformatics methods to identify the effects of SARS-CoV-2 and influenza viruses on the regulation of gene expression in patients. Front. Immunol. 14: 1098688. https://doi.org/10.3389/fimmu.2023.1098688. View in Article CrossRef Google Scholar
[42]	Li, S., Zhu, Z., Yang, F., et al. (2021). Porcine Epidemic Diarrhea Virus Membrane Protein Interacted with IRF7 to Inhibit Type I IFN Production during Viral Infection. J. Immunol. 206(12): 2909–2923. https://doi.org/10.4049/jimmunol.2001186. View in Article CrossRef Google Scholar
[43]	Dong, H., Wu, W., Li, J., et al. (2022). PML Body Component Sp100A Is a Cytosolic Responder to IFN and Activator of Antiviral ISGs. mBio 13(6): e0204422. https://doi.org/10.1128/mbio.02044-22. View in Article CrossRef Google Scholar
[44]	Brodin, P., and Davis, M.M. (2017). Human immune system variation. Nat. Rev. Immunol. 17(1): 21–29. https://doi.org/10.1038/nri.2016.125. View in Article CrossRef Google Scholar
[45]	Imai, K., Keele, L., and Tingley, D. (2010). A general approach to causal mediation analysis. Psychol. Methods 15(4): 309–334. https://doi.org/10.1037/a0020761. View in Article CrossRef Google Scholar
[46]	Rubin, D.B. (2005). Causal Inference Using Potential Outcomes: Design, Modeling, Decisions. J. Am. Stat. Assoc. 100(March): 322–331. https://doi.org/10.1198/016214504000001880. View in Article CrossRef Google Scholar
[47]	Wang, B., Li, J., Wu, S., et al. (2023). A seroepidemiological survey of adenovirus type 7 circulation among healthy adults in China and in Sierra Leone, West Africa. Front. Public Health 11: 1095343. https://doi.org/10.3389/fpubh.2023.1095343. View in Article CrossRef Google Scholar
[48]	Li, S., Rouphael, N., Duraisingham, S., et al. (2014). Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat Immunol 15(2): 195–204. https://doi.org/10.1038/ni.2789. View in Article CrossRef Google Scholar
[49]	Böhnke, J.R. (2016). Explanation in causal inference: Methods for mediation and interaction. Q. J. Exp. Psychol. 69(6): 1243–1244. https://doi.org/10.1080/17470218.2015.1115884. View in Article CrossRef Google Scholar
[50]	Manski, C.F. (2007). Identification for Prediction and Decision (Harvard University Press), p. 368. https://doi.org/10.4159/9780674033665. View in Article Google Scholar
[51]	Anderson, M.J. (2017). Permutational Multivariate Analysis of Variance (PERMANOVA) (Wiley StatsRef: Statistics Reference Online), pp. 557–574. https://doi.org/10.1002/9781118445112.stat07841. View in Article Google Scholar

Cited by

ABOUT THIS ARTICLE

Cite this article:

Zhang Z., Yang W., Chen Z., et al., (2024). A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients. The Innovation 5(3), 100603. https://doi.org/10.1016/j.xinn.2024.100603

Zhang Z., Yang W., Chen Z., et al., (2024). A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients. The Innovation 5(3), 100603. https://doi.org/10.1016/j.xinn.2024.100603

Welcome!

To request copyright permission to republish or share portions of our works, please visit Copyright Clearance Center's (CCC) Marketplace website at marketplace.copyright.com.

PDF

Figures(5)

Supplementary Information

download_supplementary
A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients

Article Metrics

Article views(3224) PDF downloads(1806)

A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients

GRAPHICAL ABSTRACT

PUBLIC SUMMARY

ABSTRACT