Magnitude Of Antibody Cross-Reactivity In Medically Important Mosquito-Borne Flaviviruses: A Systematic Review (Suburban Journal Club)

July 09,2022
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Journal Article: Magnitude Of Antibody Cross-Reactivity In Medically Important Mosquito-Borne Flaviviruses: A Systematic Review

Journal: Infection and Drug Resistance, volume 14; pg no: 4291-4299

DOI: 10.2147/IDR.S336351

Flaviviruses are enveloped single-stranded RNA viruses belonging to the genus Flavivirus and family Flaviviridae. There are 53 recognized flavivirus spp., of which 40 are known to cause disease in humans.

The major human pathogenic viruses under this genera include:

Dengue Virus (DENV)
Japanese Encephalitis Virus (JEV)
Zika Virus (ZIKV)
Yellow Fever Virus (YFV)
West Nile Virus (WNV)

Other viruses belonging to this genus may cause hemorrhagic fever and encephalitis.

These viruses are considered arboviruses, and are transmitted via mosquito bites. DENV alone infects >100 million people annually, and 500,000 people suffer from dengue fever.

While many flavivirus infections are asymptomatic, they may begin as an aspecific febrile illness and develop into a severe and life-threatening disease.

The flavivirus genome encodes three structural proteins required for the formation of virus particles:

Capsid [C]
Premembrane/membrane [prM/M]
Envelope [E]

The genome also encodes 7 nonstructural (NS) proteins that are not part of infectious virus particles, but are critical for replication of viral RNA by suppressing antiviral defense responses mounted by the host after expression in infected cells:

NS1
NS2A
NS2B
NS3
NS4A
NS4B
NS5

Cross-reaction of DENV with other flaviviruses:

Target flavivirus	Cross-reaction with Abs produced against	Source of sample (serum)	Assay type	Cross-reaction (%)
DENV2	YFV and/or JEV	JEV- and YFV-vaccinated	PRNT50 (titer at least 1:20)	38.5
DENV	JEV	JEV patients	PRNT50 (titer at least 1:10)	15.4
DENV1–4	YFV and/or JEV	JEV patients immunized with YFV 17D vaccine	PRNT50 (titer at least 1:10)	33.3
DENV	YFV	YFV-vaccinated (17D vaccine)	IgG ELISA	15.1
DENV	TBEV	TBEV-vaccinated	IgG ELISA	23.1
DENV	ZIKV	ZIKV-infected travellers	DENV NS1 antigen ELISA	—
DENV	ZIKV	ZIKV-infected travellers	IgM ELISA	31
DENV	ZIKV	ZIKV-infected travellers	IgG ELISA	54
DENV	YFV	YFV patients	IgG ELISA	76.9
DENV	YFV	YFV patients	IgM ELISA	46.2
DENV	YFV	YFV vaccines	IgM ELISA	42.1
DENV	Non-dengue flaviviruses	YFV/WNV/JEV patients and TBEV vaccines	IgM IFA	33
DENV	Non-dengue flaviviruses	YFV/WNF/JEV patients and TBEV vaccines	IgG IFA	71
DENV	Non-dengue flaviviruses	YFV/WNF/JEV patients and TBEV vaccines	IgM EIA	39
DENV	Non-dengue flaviviruses	YFV/WNF/JEV patients and TBEV vaccines	IgG EIA	84
DENV	YFV	YFV vaccinated	IgG ELISA	3.9

DENV - Dengue Virus; JEV - Japanese Encephalitis Virus; TBEV - Tick Borne Encephalitis Virus; WNV - West Nile Virus; YFV - Yellow fever Virus; ZIKV - Zika Virus

Highest cross-reactions were observed between:
DENV and YFY
DENV and ZIKV
The highest cross-reactivity was demonstrated with IgG-capture assays (ELISA/IFA/EIA) compared to IgM-capture assays (ELISA/IFA/EIA).
Animal-model studies on closely related flaviviruses also demonstrated that IgG-based assays were less specific than IgM-based assays for homologous viruses.
Assays based on the E protein compared to those based on the NS1 protein led to higher cross-reactivity

The full article with details about the cross-reactivity of other medically relevant flaviviruses can be accessed at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541746/