Immunological Assays used to Support Efficacy of Zika Virus Vaccines
Abstract
:1. Introduction
2. Assessment of the Humoral Immune Response to ZIKV Vaccines
2.1. Functional Assays
2.2. Binding Assays
3. Assessment of the Cell-Mediated Immune Response to ZIKV Vaccines
3.1. Intracellular Cytokine Staining
3.2. ELISpot Assays
4. Pre-Clinical Assessment of ZIKV Vaccines in Animal Immunization/Challenge Models
4.1. Active Immunization
4.2. Passive Immunization
5. Standardization of Assays
6. Complementary Assays That Support ZIKV Vaccine Efficacy
7. How Assays Can be Used for Licensure
8. Use of the US FDA Animal Rule for Establishing Vaccine Efficacy
9. Human Challenge Studies
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Dowd, K.A.; DeMaso, C.R.; Pelc, R.S.; Speer, S.D.; Smith, A.R.; Goo, L.; Platt, D.J.; Mascola, J.R.; Graham, B.S.; Mulligan, M.J.; et al. Broadly neutralizing activity of Zika virus-immune sera identifies a single viral serotype. Cell Rep. 2016, 16, 1485–1491. [Google Scholar] [CrossRef] [PubMed]
- Lazear, H.M.; Diamond, M.S. Zika virus: New clinical syndromes and its emergence in the western hemisphere. J. Virol. 2016, 90, 4864–4875. [Google Scholar] [CrossRef] [PubMed]
- Cao-Lormeau, V.M.; Blake, A.; Mons, S.; Lastere, S.; Roche, C.; Vanhomwegen, J.; Dub, T.; Baudouin, L.; Teissier, A.; Larre, P.; et al. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study. Lancet 2016, 387, 1531–1539. [Google Scholar] [CrossRef]
- Kleber de Oliviera, W.; Araujo de Franca, G.V.; Carmo, E.H.; Duncan, B.B.; de Souza Kuchenbecker, R.; Schmidt, M.I. Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: A surveillance-based analysis. Lancet 2017, 390, 861–870. [Google Scholar] [CrossRef]
- Gubler, D.J.; Vasilakis, N.; Musso, D. History and emergence of Zika virus. J. Infect. Dis. 2017, 216, S860–S867. [Google Scholar] [CrossRef] [PubMed]
- Barouch, D.H.; Thomas, S.J.; Michael, N.L. Prospects for a Zika virus vaccine. Immunity 2017, 46, 176–182. [Google Scholar] [CrossRef] [PubMed]
- Mason, R.A.; Tauraso, N.M.; Spertzel, R.O.; Ginn, R.K. Yellow fever vaccine: Direct challenge of monkeys given graded doses of 17D vaccine. Appl. Microbiol. 1973, 25, 539–544. [Google Scholar]
- Hombach, J.; Solomon, T.; Kurane, I.; Jacobson, J.; Wood, D. Report of a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, Switzerland, 2–3 September 2004. Vaccine 2005, 23, 5205–5211. [Google Scholar] [CrossRef]
- Plotkin, S.A. Correlates of protection induced by vaccination. Clin. Vaccine Immunol. 2010, 17, 1055–1065. [Google Scholar] [CrossRef]
- Thakur, A.; Pedersen, L.E.; Jungersen, G. Immune markers and correlates of protection for vaccine induced immune responses. Vaccine 2012, 30, 4907–4920. [Google Scholar] [CrossRef]
- Subchareon, A.; Sirivichayakul, W.D.; Limkittikul, K.; Chanthavanich, P.; Suvannadabba, S.; Jiwariyavei, V.; Dulyachai, W.; Pengsaa, K.; Wartel, T.A.; Moureau, A.; et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: A randomized, controlled phase 2b trial. Lancet 2012, 380, 1559–1567. [Google Scholar] [CrossRef]
- Dowd, K.A.; Ko, S.-Y.; Morabito, K.M.; Yang, E.S.; Pelc, R.S.; DeMaso, C.R.; Castilho, L.R.; Abbink, P.; Boyd, M.; Nityanandam, R.; et al. Rapid development of a DNA vaccine for Zika virus. Science 2016, 354, 1290–1301. [Google Scholar] [CrossRef] [PubMed]
- Gaudinski, M.R.; Houser, K.V.; Morabito, K.M.; Hu, Z.; Yamshchikov, G.; Rothwell, R.S.; Berkowitz, N.; Mendoza, F.; Saunders, J.G.; Novik, L.; et al. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: Randomized, open-label, phase 1 clinical trials. Lancet 2018, 391, 552–562. [Google Scholar] [CrossRef]
- Tebas, P.; Roberts, C.C.; Muthumani, K.; Reuschel, E.L.; Kudchodkar, S.B.; Zaidi, F.I.; White, S.; Khan, A.S.; Racine, T.; Choi, H.; et al. Safety and Immunogenicity of an Anti–Zika Virus DNA Vaccine — Preliminary Report. N. Engl. J. Med. 2017. [Google Scholar] [CrossRef] [PubMed]
- Muthumani, K.; Griffin, B.D.; Agarwal, S.; Kudchodkar, S.B.; Reuschel, E.L.; Choi, H.; Kraynyak, K.A.; Duperret, E.K.; Keaton, A.A.; Chung, C.; et al. In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunization with a prMEnv DNA vaccine. NPJ Vaccines 2016, 1, 16021. [Google Scholar] [CrossRef] [PubMed]
- Larocca, R.A.; Abbink, P.; Peron, J.P.; Paolo, M.D.; Iampietro, M.J.; Badamchi-Zadeh, A.; Boyd, M.; Kirilova, M.; Nityanandam, R.; Mercado, N.B.; et al. Vaccine protection against Zika virus from Brazil. Nature 2016, 536, 474–478. [Google Scholar] [CrossRef] [PubMed]
- Abbink, P.; Larocca, R.A.; Visitsunthorn, K.; Boyd, M.; De LA Barrera, R.A.; Gromowski, G.D.; Kirilova, M.; Peterson, R.; Li, Z.; Nanayakkara, O.; et al. Durability and correlates of vaccine protection against Zika virus in rhesus monkeys. Sci. Transl. Med. 2017, 9. [Google Scholar] [CrossRef] [Green Version]
- Modjarrad, K.; Lin, L.; George, S.L.; Stephenson, K.E.; Eckels, K.H.; De La Barrera, R.A.; Jarman, R.G.; Sondergaard, E.; Tennant, J.; Ansel, J.L.; et al. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: Phase 1, randomized, double-blind, placebo-controlled clinical trials. Lancet 2017, 391, 563–571. [Google Scholar] [CrossRef]
- Abbink, P.; Larocca, R.A.; De La Barrera, R.A.; Bricault, C.A.; Moseley, E.T.; Boyd, M.; Kirilova, M.; Li, Z.; Ngang’a, D.; Nanayakkara, O.; et al. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science 2016, 353, 1129–1132. [Google Scholar] [CrossRef] [Green Version]
- Sumathy, K.; Kulkarni, B.; Gondu, R.K.; Ponnuru, S.K.; Bonguram, N.; Eligeti, R.; Gadiyaram, S.; Praturi, U.; Chougule, B.; Karunakaran, L.; et al. Protective efficacy of Zika vaccine in AG129 mouse model. Sci. Rep. 2017, 7, 1–9. [Google Scholar] [CrossRef]
- Richner, J.M.; Himansu, S.; Dowd, K.A.; Butler, S.L.; Salazar, V.; Fox, J.M.; Julander, J.G.; Tang, W.W.; Shresta, S.; Pierson, T.C.; et al. Modified mRNA vaccines protect against Zika virus infection. Cell 2016, 168, 1114–1125. [Google Scholar] [CrossRef] [PubMed]
- Cox, F.; van der Fits, L.; Abbink, P.; Larocca, R.A.; van Huizen, E.; Saeland, E.; Verhagen, J.; Peterson, R.; Tolboom, J.; Kaufmann, B.; et al. Adenoviral vector type 26 encoding Zika virus (ZIKV) M-Env antigen induces humoral and cellular immune responses and protects mice and nonhuman primates against ZIKV challenge. PLoS ONE 2018, 13, e020282. [Google Scholar] [CrossRef] [PubMed]
- Pierson, T.C.; Sanchez, M.D.; Puffer, B.A.; Ahmed, A.A.; Geiss, B.J.; Valentine, L.E.; Altamura, L.A.; Diamond, M.S.; Doms, R.W. A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection. Virology 2006, 346, 53–65. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wilson, H.L.; Tran, T.; Druce, J.; Dupont-Rouzeyroi, M.; Catton, M. Neutralization assay for Zika and dengue viruses by use of real-time-PCR-based endpoint assessment. J. Clin. Microbiol. 2017, 55, 3104–3112. [Google Scholar] [CrossRef] [PubMed]
- Zhao, H.; Fernandez, E.; Dowd, K.A.; Speer, S.D.; Platt, D.J.; Gorman, M.J.; Govero, J.; Nelson, C.A.; Pierson, T.C.; Diamond, M.S.; et al. Structural basis of Zika virus-specific antibody protection. Cell 2016, 166, 1016–1027. [Google Scholar] [CrossRef] [PubMed]
- Martinez, L.J.; Lin, L.; Blaylock, J.M.; Lyons, A.G.; Bauer, K.M.; De La Barrera, R.; Simmons, M.; Jarman, R.G.; Currier, J.R.; Friberg, H.; et al. Safety and immunogenicity of a dengue virus serotype-1 purified-inactivated vaccine: Results of a phase 1 clinical trial. Am. J. Trop. Med. Hyg. 2015, 93, 454–460. [Google Scholar] [CrossRef] [PubMed]
- Sun, W.; Nisalak, A.; Gettayacamin, M.; Eckels, K.H.; Putnak, J.R.; Vaughn, D.W.; Innis, B.L.; Thomas, S.J.; Endy, T.P. Protection of Rhesus monkeys against dengue virus challenge after tetravalent live-attenuated dengue virus vaccination. J. Infect. Dis. 2006, 193, 1658–1665. [Google Scholar] [CrossRef]
- Putnak, J.R.; Coller, B.A.; Voss, G.; Vaughn, D.W.; Clements, D.; Peters, I.; Bignami, G.; Houng, H.S.; Chen, R.C.; Barvir, D.A.; et al. An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model. Vaccine 2005, 23, 4442–4452. [Google Scholar] [CrossRef]
- Page, M.; Mattiuzzo, G.; Hassall, M.; Ashall, J.; Myhill, S.; Faulkner, V.; Hockley, J.; Atkinson, D.; Rigsby, P.; Efstathiou, S.; et al. Developing biological standards for vaccine evaluation. Future Virol. 2018, 12, 431–437. [Google Scholar] [CrossRef]
- Slifka, M.K.; Antia, R.; Whitmire, J.K.; Ahmed, R. Humoral immunity due to long-lived plasma cells. Immunity 1998, 8, 363–372. [Google Scholar] [CrossRef]
- Brynjolfsson, S.F.; Berg, L.P.; Ekerhult, T.A.; Rimkute, I.; Wick, M.-J.; Martensson, I.-L.; Grimsholm, O. Long-lived plasma cells in mice and men. Front. Immunol. 2018, 9, 2673. [Google Scholar] [CrossRef] [PubMed]
- Terzian, A.C.B.; Schanoski, A.S.; Mota, M.T.O.; da Silva, R.A.; Estofolete, C.F.; Colombo, T.E.; Rahal, P.; Hanley, K.A.; Vasilakis, N.; Kalil, J.; et al. Viral load and cytochrome response profile does not support antibody-dependent enhancement in dengue-primed Zika virus-infected patients. Clin. Infect. Dis. 2017, 65, 1260–1265. [Google Scholar] [CrossRef] [PubMed]
- George, J.; Valiant, W.G.; Mattapallil, M.J.; Walker, M.; Huang, Y.-J.S.; Vanlandingham, D.L.; Misamore, J.; Greenhouse, J.; Weiss, D.E.; Verthelyi, S.; et al. Prior exposure to Zika virus significantly enhances peak dengue-2 viremia in rhesus macaques. Sci. Rep. 2017, 7, 10498. [Google Scholar] [CrossRef] [PubMed]
- Gruber, M.F.; Krause, P.R. Regulating vaccines at the FDA: Development and licensure of Zika vaccines. Exp. Rev. Vaccines 2017, 16, 525–527. [Google Scholar] [CrossRef] [PubMed]
- Hoke, C.H.; Nisalak, A.; Sangawhipa, N.; Jatanasen, S.; Laorakapongse, T.; Innis, B.L.; Kotchasenee, S.; Gingrich, J.B.; Latendresse, J.; Fukai, K.; et al. Protection against Japanese encephalitis by inactivated vaccines. N. Engl. J. Med. 1988, 319, 608–614. [Google Scholar] [CrossRef] [PubMed]
- Code of Federal Regulations 21 Part 601. 2016. Available online: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=601&showFR=1&subpartNode=21:7.0.1.1.2.5 (accessed on 20 May 2018).
- Product Development under the Animal Rule: Guidance for Industry. Available online: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/product-development-under-animal-rule (accessed on 21 May 2019).
- Dudley, D.M.; Aliota, M.T.; Mohr, E.L.; Weiler, A.M.; Lehrer-Brey, G.; Weisgrau, K.L.; Mohns, M.S.; Breitbach, M.E.; Rasheed, M.N.; Newman, C.M.; et al. A rhesus macaque model of Asian-lineage Zika virus infection. Nat. Commun. 2016, 7, 12204. [Google Scholar] [CrossRef] [PubMed]
- Li, X.-F.; Dong, H.-L.; Huang, X.-Y.; Qiu, Y.-F.; Wang, H.-J.; Deng, Y.-Q.; Zhang, N.-N.; Ye, Q.; Zhao, H.; Liu, Z.-Y.; et al. Characterization of a 2016 clinical isolate of Zika virus in non-human primates. EBioMedicine 2016, 12, 170–177. [Google Scholar] [CrossRef] [PubMed]
- Martinot, A.J.; Abbink, P.; Afacan, O.; Prohl, A.K.; Bronson, R.; Hecht, J.L.; Borducchi, E.N.; Larocca, R.A.; Peterson, R.L.; Rinaldi, W.; et al. Fetal neuropathology in Zika virus-infected pregnant female rhesus monkeys. Cell 2018, 173, 1111–1122. [Google Scholar] [CrossRef] [PubMed]
- Durbin, A.P.; Whitehead, S.S. Zika vaccines: Role for controlled human infection. J. Infect. Dis. 2017, 216, 971–975. [Google Scholar] [CrossRef] [PubMed]
- Kirkpatrick, B.D.; Whitehead, S.S.; Pierce, K.K.; Tibery, C.M.; Grier, P.L.; Hynes, N.A.; Larsson, C.J.; Sabundayo, B.P.; Talaat, K.R.; Janiak, A.; et al. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Sci. Trans. Med. 2016, 8, 330–336. [Google Scholar] [CrossRef]
Vaccine Developer/Collaborator | Vaccine/Clinical Trial | Pre-Clinical Assays | Clinical Assays | References |
---|---|---|---|---|
Vaccine Research Center (NIAID) | DNA NCT02840487 NCT02996461 NCT03110770 | Neutralization (reporter virus particle, focus-reduction, and ELISA MN50)); ELISA with subviral particles; immunogenicity in Balb/c and C5BL/6 mice; immunogenicity and efficacy in NHP’s | Neutralization (reporter virus particle); CMI (intracellular cytokine staining) | [12,13] |
GeneOne Life Sciences/Inovio Pharmaceuticals, The Wistar Institute | DNA NCT02809443 | Neutralization (PRNT50); ELISA (E-specific); CMI (intracellular cytokine staining, IFN ELISpot); immunogenicity and efficacy in C57BL/6 and IFNAR-/- mice; immunogenicity in NHPs | Neutralization (immunofluorescense MN50); ELISA; CMI (IFN ELISpot); passive protection in IFNAR mice using vaccinee sera | [14,15] |
WRAIR, Beth Israel Deaconess Medical Center, NIAID | Inactivated NCT02963909 NCT02952833 NCT02937233 NCT03008122 | Neutralization (ELISA MN50); CMI (ELISpot, Intracellular cytokine staining); efficacy in Balb/c mice and NHPs; ELISA (E-specific); passive protection in NHPs | Neutralization (ELISA MN50); passive protection in mice using vaccinee sera | [16,17,18,19] |
Bharat Biotech | Inactivated CTRI/2017/05/008539 | Neutralization (PRNT50); ELISA (inactivated vaccine-specific); efficacy in AG129 mice; immunogenicity in Balb/c mice; passive immunization in Balb/c mice | NP1 | [20] |
Takeda | Inactivated NCT03343626 | NP | NP | |
Valneva/EmergentBiosolutions | Inactivated NCT03425149 | NP | NP | |
Valera/Moderna | mRNA NCT03014089 | Neutralization (PRNT50, FRNT50, reporter virus particle) | NP | [21] |
Themis | Measles-vectored NCT02996890 | NP | NP | |
NIAID/NIH | Live-attenuated (chimeric) NCT03611946 | NP | NP | |
Janssen | Vectored Ad26 E/M NCT03356561 | Neutralization (FRNT50); ELISA (E-specific); CMI (IFN ELISpot; intracellular cytokine staining); immunogenicity and challenge in Balb/c mice; immunogenicity and challenge in rhesus macaques | NP | [17,19,22] |
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Eckels, K.H.; De La Barrera, R.A.; Putnak, J.R. Immunological Assays used to Support Efficacy of Zika Virus Vaccines. Trop. Med. Infect. Dis. 2019, 4, 97. https://doi.org/10.3390/tropicalmed4030097
Eckels KH, De La Barrera RA, Putnak JR. Immunological Assays used to Support Efficacy of Zika Virus Vaccines. Tropical Medicine and Infectious Disease. 2019; 4(3):97. https://doi.org/10.3390/tropicalmed4030097
Chicago/Turabian StyleEckels, Kenneth H., Rafael A. De La Barrera, and Joseph Robert Putnak. 2019. "Immunological Assays used to Support Efficacy of Zika Virus Vaccines" Tropical Medicine and Infectious Disease 4, no. 3: 97. https://doi.org/10.3390/tropicalmed4030097
APA StyleEckels, K. H., De La Barrera, R. A., & Putnak, J. R. (2019). Immunological Assays used to Support Efficacy of Zika Virus Vaccines. Tropical Medicine and Infectious Disease, 4(3), 97. https://doi.org/10.3390/tropicalmed4030097