Epitope of dengue virus E protein detect human antibodies associated with mild disease: a potential peptide for vaccine development

Sánchez-Burgos, Gilma Guadalupe; Herrera-Nájera, Carla; Cedillo‐Rivera, Roberto; Dumonteil, Eric

doi:10.1016/j.bjid.2019.10.009

Cited by 2 publications

(3 citation statements)

References 10 publications

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“…In this review, we have described a range of linear immunoreactive peptides that may be useful for disease prognosis, such as Pep32 from DIII of the DENV1 envelope protein, which demonstrated a positive IgG detection signal for sera from patients with mild DENV disease. However, patients progressing to a more severe disease state demonstrated very limited IgG detection using this peptide; therefore, it could be used as a biological marker of disease severity for DENV infection (Sanchez-Burgos et al, 2020). Additionally, five peptides from two regions of the DENV2 Ns1 protein (Pep104, Pep106, Pep109, Pep118, and Pep119) were suggested to be biological markers of DF, DHF, and DSS (Hertz et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that the peptide may be a pan-flavivirus epitope with immunodiagnostic potential. Furthermore, another study predicted and evaluated a linear epitope from DIII of the envelope protein region of DENV1 (Pep32, RGARRMAIL), which is 89% conserved among the four DENV serotypes (Sanchez-Burgos et al, 2020). This study demonstrated that Pep32 reacted at a high frequency with IgG antibodies from DENV patients showing no warning symptoms or with mild disease during the early phase of infection; however, the peptide only showed a very limited detection frequency when IgG from patients with severe disease was used.…”

Section: Envelope Proteinmentioning

confidence: 99%

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Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans

Fumagalli

Figueiredo

Aquino

2021

Front. Cell. Infect. Microbiol.

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This manuscript is an up-to-date review of experimentally validated linear and continuous epitopes identified from arbovirus members of the Flavivirus genus. We summarized 153 immunoreactive peptides from the Dengue virus, Zika virus, Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus described in studies published from 1989 to 2020. We included peptides from structural (envelope, capsid, and pre-membrane) and nonstructural (Ns1–5) viral proteins that demonstrated relevant immunoreactivity with antibodies from naturally infected or vaccinated humans. We included peptides that demonstrated relevant reactivity features, such as indicators of disease severity related to immunological or immunopathological outcomes, differential or group diagnostic markers, immunotherapy candidates, and potential for vaccine formulation. The majority of immunoreactive peptides were described for DENV probably due to its long-lasting impact on human health and the lack of efficient vaccines and therapeutic methods. Immune landscape data regarding linear immunoreactive and continuous flavivirus peptides are still scarce, and a complete and more detailed map remains to be elucidated. Therefore, this review provides valuable data for those investigating the antibody response against flavivirus infection.

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Section: Discussionmentioning

confidence: 99%

Section: Envelope Proteinmentioning

confidence: 99%

Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans

Fumagalli

Figueiredo

Aquino

2021

Front. Cell. Infect. Microbiol.

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“…A recent study showed that the fusion loops of envelope protein domain II, which is highly conserved in flaviviruses, are the predominant target of cross-neutralizing antibodies in the DENV serotypes. Thus, this epitope is a promising target for developing treatments [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Generation and therapeutic efficacy of the novel Fc-modified cross-neutralizing human monoclonal antibodies against dengue virus

Injampa

Benjathummarak

Keadsanti

et al. 2023

Preprint

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Background Dengue disease is a mosquito-borne infection caused by four dengue virus serotypes (DENV1-4). Secondary infections can produce flavivirus cross-reactive antibodies at sub-neutralizing levels. This phenomenon can significantly increase the severity of secondary infections via antibody-dependent enhancement (ADE). ADE activity is associated with a high risk of viral infection in immune effector cells, triggering cytokine cascade and activating the complement system, which lead to severe symptoms. Despite extensive studies, therapeutic antibodies, particularly fully human monoclonal antibodies, which can be an option for immune passive therapy, have not yet been discovered. Methodology/Principal Findings This study generated LALA-mutated human monoclonal antibody clone B3B9 (LALA-B3B9 HuMAb) that can neutralize all four DENV serotypes without enhancing viral activity. The number of infected cells obtained with the ADE assay was compared among wild-type antibody (B3B9), and modified Fc, LALA-B3B9 HuMAb, and N297Q (N297Q-B3B9), with or without complement proteins. Moreover, the therapeutic efficacy of these HuMAbs against ADE infection by competing with natural antibodies in patients with acute dengue was determined using the in vitro suppression-of-enhancement assay in K562 cells. The novel Fc-modified antibody LALA-B3B9 (Leu234Ala/Leu235Ala mutations) could have a therapeutic effect. Further, it exhibited neutralization properties against all dengue virus serotypes without triggering ADE activity at any antibody concentration. This outcome was similar to that of the previous Fc-modified N297Q-B3B9 antibody (N297Q mutation). Moreover, the effect of complement protein on enhancing and neutralizing activities was evaluated to assess unwanted inflammatory responses to these therapeutic antibodies. Results showed that the elimination of complement activity could reduce the severity of dengue. The activities of LALA-B3B9 and N297Q-B3B9 HuMAbs were complement-independent in all dengue virus serotypes. Conclusions LALA-B3B9 and N297Q-B3B9 HuMAbs can prevent the suppression-of-enhancement activity in K562 cells caused by human DENV2. Hence, they are promising candidates for dengue treatment.

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Epitope of dengue virus E protein detect human antibodies associated with mild disease: a potential peptide for vaccine development

Cited by 2 publications

References 10 publications

Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans

Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans

Generation and therapeutic efficacy of the novel Fc-modified cross-neutralizing human monoclonal antibodies against dengue virus

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