CD4+ T cells Promote Humoral Immunity and Viral Control during Zika Virus Infection

Ngono, Annie Elong; Young, Matthew P.; Bunz, Maximilian; Xu, Zhiyuan; Hattakam, Sararat; Vizcarra, Edward A.; Regla-Nava, José Ángel; Tang, William W.; Yamabhai, Montarop; Wen, Jinsheng; Shresta, Sujan

doi:10.4049/jimmunol.202.supp.140.15

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…For example, while truncated prokaryote-expressed E ZIKV (30) or EDIII ZIKV (31) were shown to induce high titers of neutralizing antibodies, no difference in immunogenicity and protection were obtained when a version of the E protein (E80) was produced in eukaryotic and prokaryotic systems (40). CD4 + T cells is essential for the protective immunity against ZIKV, since their depletion reduced the generation of anti-ZIKV antibodies (50,60) and CD8 + T cell responses (61). Furthermore, CD8 + T cells are important during flavivirus infections as they contribute to protection in B cell-deficient mice (51), and their lack increases mortality in ZIKVinfected mice (62).…”

Section: Discussionmentioning

confidence: 99%

“…The results of a phase 1 clinical trial of a ZIKV inactivated vaccine demonstrated that neutralizing antibody response declined significantly by week 16 (52). The sharp drop in neutralizing antibody titers may be related to the poor ability of the inactivated vaccine to induce cellular immune responses, particularly the lack of CD8 + T cells (50). Here, immunization with all ZIKV envelope proteins induced specific IFNg-producing cells as well as CD4 + and CD8 + T cells able to produce IFNg or TNFa, in a similar way.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells

et al. 2023

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IntroductionIn the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes.MethodsIn this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV.ResultsTesting of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses.ConclusionIn conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells

et al. 2023

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“…While neutralizing antibodies are the primary correlates of protection against ZIKV, T cell immunity also plays an important role in controlling Zika infection [ 66 ]. Several experimental mouse models have explored the role of T cells in ZIKV protection [ 67 , 68 , 69 ]. Since cytokines play a key role in activating the immune system and generating an effective immune response, the identification of ZIKV-specific cytokines can help in the selection of target antigens and vaccine formulations.…”

Section: Discussionmentioning

confidence: 99%

Production of Recombinant Zika Virus Envelope Protein by Airlift Bioreactor as a New Subunit Vaccine Platform

da Costa,

Bielavsky,

Orts

et al. 2023

IJMS

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The Zika Virus (ZIKV) is an emerging arbovirus of great public health concern, particularly in the Americas after its last outbreak in 2015. There are still major challenges regarding disease control, and there is no ZIKV vaccine currently approved for human use. Among many different vaccine platforms currently under study, the recombinant envelope protein from Zika Virus (rEZIKV) constitutes an alternative option for vaccine development and has great potential for monitoring ZIKV infection and antibody response. This study describes a method to obtain a bioactive and functional rEZIKV using an E. coli expression system, with the aid of a 5-L airlift bioreactor and following an automated fast protein liquid chromatography (FPLC) protocol, capable of obtaining high yields of approximately 20 mg of recombinant protein per liter of bacterium cultures. The purified rEZIKV presented preserved antigenicity and immunogenicity. Our results show that the use of an airlift bioreactor for the production of rEZIKV is ideal for establishing protocols and further research on ZIKV vaccines bioprocess, representing a promising system for the production of a ZIKV envelope recombinant protein-based vaccine candidate.

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“…Full protection against flaviviruses involves a combination of adaptive humoral and cellular responses [ 22 ]. Since many immunodominant epitopes for the induction of T cell-mediated responses are present in non-structural proteins, epitopes or domains of proteins, such as NS1 and NS3, have been included in the design of vaccines, targeting both ZIKV and DENV [ 23 ]. In this context, vaccines based on multiepitope sequences are promising platforms concerning immunogenicity, protection, and safety [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model

et al. 2023

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Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for antigen delivery, in addition to their adjuvant properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. The development of these prophylactic strategies is fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, in addition to the activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here, we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct using yeast as a delivery system and reinforcing the applicability of P. pastoris as a whole-cell vaccine.

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CD4+ T cells Promote Humoral Immunity and Viral Control during Zika Virus Infection

Cited by 5 publications

References 39 publications

Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells

Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells

Production of Recombinant Zika Virus Envelope Protein by Airlift Bioreactor as a New Subunit Vaccine Platform

Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model

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