Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

Parasites & Vectors
R A WilsonWilliam Castro-Borges

Abstract

The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co-administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40-50%. We contend that the low level of maturation of penetrating cercariae (~32% for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naïve mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation-attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNγ and TNFα, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and th...Continue Reading

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Citations

Jul 13, 2018·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Weidong ZhangAfzal A Siddiqui
Oct 8, 2016·Parasites & Vectors·Biniam Mathewos TebejeDonald P McManus
Feb 23, 2020·Seminars in Immunopathology·Donald P McManusHong You
Feb 23, 2020·PLoS Neglected Tropical Diseases·Ester Alves MotaRenata Guerra-Sá
Mar 11, 2020·Frontiers in Cellular and Infection Microbiology·Michael W MelkusAfzal A Siddiqui
Jan 24, 2020·Journal of Biomedical Science·Adebayo J Molehin
Dec 22, 2017·Emerging Topics in Life Sciences·R Alan WilsonWilliam Castro-Borges
Nov 12, 2020·Research and Reports in Tropical Medicine·Adebayo J Molehin
Dec 20, 2020·Nature Communications·Carmen Lidia Diaz SoriaMatthew Berriman
Mar 23, 2021·Frontiers in Immunology·Emmanuella DriciruMeta Roestenberg
Feb 20, 2021·The Journal of Infectious Diseases·Hannah W WuJonathan D Kurtis
May 7, 2021·Frontiers in Immunology·Emma L HoulderAndrew S MacDonald
May 11, 2021·Frontiers in Immunology· AnisuzzamanClarissa Prazeres da Costa

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Datasets Mentioned

BETA
AAC61764.1

Methods Mentioned

BETA
electron microscopy

Software Mentioned

Bepipred

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