Vaccine-Induced Adverse Effects in Cultured Neuroblastoma 2A (N2A) Cells Duplicate Toxicity of Serum from Patients with Gulf War Illness (GWI) and Are Prevented in the Presence of Specific Anti-Vaccine Antibodies.

Effie-Photini Tsilibary,Lisa James,Eric Souto,Brian Engdahl,Apostolos Georgopoulos,Marian Kratzke

doi:10.3390/vaccines8020232

Effie-Photini Tsilibary, Lisa James + Show 4 more

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https://doi.org/10.3390/vaccines8020232

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Abstract

Gulf War illness (GWI) is a chronic disease of unknown etiology affecting over 200,000 veterans with symptoms including neurocognitive problems. We previously demonstrated GWI serum toxicity on neural cell cultures manifested by compromised neural network function, decreased cell spreading, and enhanced cell apoptosis. These patients lacked six human leukocyte antigen (HLA) class II alleles, resulting in an inability to form antibodies. Therefore, we hypothesized that GWI patients have vaccine-derived, persistent pathogens, which contribute to the development of the disease. Here, we examined whether individual vaccines were toxic in cultured N2A cells. Moreover, we used antibodies against each of the 20 vaccines administered to Gulf War (GW) veterans, to examine the effects of these antibodies on cell spreading and apoptosis in N2A cells. Antibodies against cholera toxin, hepatitis B, hemagglutinin H1N1, H3N2, and B from influenza A and B strains, measles, and Salmonella Typhi polysaccharide Vi had a remarkable protective effect on both cell spreading and apoptosis, whereas none of the other antibodies administered to GW veterans had an effect. The in vitro observed adverse effects of GWI serum may be due in part to vaccine-derived pathogens, antibodies against which had a protective effect in N2A cell cultures.

Highlights

After the Persian Gulf War of 1990–1991, about one-third (>200,000) of deployed veterans complained of a variety of chronic physical and neurocognitive symptoms [1,2,3,4], which are presently identified as Gulf War illness (GWI)
This atrophy was absent in veterans carrying the human leukocyte antigen (HLA) allele DRB1*13:02 [7], one of six HLA class 2 alleles that we reported previously as protective for GWI [8]
We examined the following: (a) whether individual vaccines were toxic in cultured N2A cells, (b) whether GWI serum toxicity duplicated toxic effects of GW-era vaccines, and (c) whether antibodies against each of the 20 vaccines administered to GW veterans had protective effects on N2A cell spreading and apoptosis

Summary

Introduction

After the Persian Gulf War of 1990–1991, about one-third (>200,000) of deployed veterans complained of a variety of chronic physical and neurocognitive symptoms [1,2,3,4], which are presently identified as Gulf War illness (GWI). We previously described a number of functional and structural brain abnormalities in GWI, such as changes in synchronous neural communication patterns [5], and the presence of subcortical brain atrophy in certain GWI patients [6] This atrophy was absent in veterans carrying the human leukocyte antigen (HLA) allele DRB1*13:02 [7], one of six HLA class 2 alleles that we reported previously as protective for GWI [8]. Vaccines 2020, 8, 232 immunity, through which external antigens are presented to CD4+ lymphocytes, leading to the production of specific antibodies by B cells to neutralize the offending antigen [9] Given these considerations, we hypothesized that the lack of HLA class II protection observed in GWI would have allowed offending antigens to persist

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