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Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response.

Abstract Ascariasis remains the most common helminth infection in humans. As an alternative or complementary approach to global deworming, a pan-anthelminthic vaccine is under development targeting Ascaris, hookworm, and Trichuris infections. As16 and As14 have previously been described as two genetically related proteins from Ascaris suum that induced protective immunity in mice when formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact protective mechanism was not well understood.
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Authors

Mayor MeshTerms
Keywords
Journal Title plos neglected tropical diseases
Publication Year Start




PMID- 28708895
OWN - NLM
STAT- MEDLINE
DA  - 20170714
DCOM- 20170801
LR  - 20170801
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 7
DP  - 2017 Jul
TI  - Yeast-expressed recombinant As16 protects mice against Ascaris suum infection
      through induction of a Th2-skewed immune response.
PG  - e0005769
LID - 10.1371/journal.pntd.0005769 [doi]
AB  - BACKGROUND: Ascariasis remains the most common helminth infection in humans. As
      an alternative or complementary approach to global deworming, a pan-anthelminthic
      vaccine is under development targeting Ascaris, hookworm, and Trichuris
      infections. As16 and As14 have previously been described as two genetically
      related proteins from Ascaris suum that induced protective immunity in mice when 
      formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact
      protective mechanism was not well understood. METHODOLOGY/PRINCIPAL FINDINGS:
      As16 and As14 were highly expressed as soluble recombinant proteins (rAs16 and
      rAs14) in Pichia pastoris. The yeast-expressed rAs16 was highly recognized by
      immune sera from mice infected with A. suum eggs and elicited 99.6% protection
      against A. suum re-infection. Mice immunized with rAs16 formulated with ISA720
      displayed significant larva reduction (36.7%) and stunted larval development
      against A. suum eggs challenge. The protective immunity was associated with a
      predominant Th2-type response characterized by high titers of serological IgG1
      (IgG1/IgG2a > 2000) and high levels of IL-4 and IL-5 produced by restimulated
      splenocytes. A similar level of protection was observed in mice immunized with
      rAs16 formulated with alum (Alhydrogel), known to induce mainly a Th2-type immune
      response, whereas mice immunized with rAs16 formulated with MPLA or AddaVax, both
      known to induce a Th1-type biased response, were not significantly protected
      against A. suum infection. The rAs14 protein was not recognized by A. suum
      infected mouse sera and mice immunized with rAs14 formulated with ISA720 did not 
      show significant protection against challenge infection, possibly due to the
      protein's inaccessibility to the host immune system or a Th1-type response was
      induced which would counter a protective Th2-type response.
      CONCLUSIONS/SIGNIFICANCE: Yeast-expressed rAs16 formulated with ISA720 or alum
      induced significant protection in mice against A. suum egg challenge that
      associates with a Th2-skewed immune response, suggesting that rAS16 could be a
      feasible vaccine candidate against ascariasis.
FAU - Wei, Junfei
AU  - Wei J
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Versteeg, Leroy
AU  - Versteeg L
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Liu, Zhuyun
AU  - Liu Z
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Keegan, Brian
AU  - Keegan B
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Gazzinelli-Guimaraes, Ana Clara
AU  - Gazzinelli-Guimaraes AC
AD  - Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo
      Horizonte, Brazil.
FAU - Fujiwara, Ricardo T
AU  - Fujiwara RT
AD  - Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo
      Horizonte, Brazil.
FAU - Briggs, Neima
AU  - Briggs N
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
AD  - The University of Texas MD Anderson Cancer Center UT Health Graduate School of
      Biomedical Sciences, Houston, Texas, United States of America.
FAU - Jones, Kathryn M
AU  - Jones KM
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Strych, Ulrich
AU  - Strych U
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Beaumier, Coreen M
AU  - Beaumier CM
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
FAU - Bottazzi, Maria Elena
AU  - Bottazzi ME
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
AD  - Department of Biology, Baylor University, Waco, Texas, United States of America.
FAU - Hotez, Peter J
AU  - Hotez PJ
AUID- ORCID: http://orcid.org/0000-0001-8770-1042
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
AD  - Department of Biology, Baylor University, Waco, Texas, United States of America.
FAU - Zhan, Bin
AU  - Zhan B
AD  - Texas Children's Hospital Center for Vaccine Development, National School of
      Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of
      America.
LA  - eng
PT  - Journal Article
DEP - 20170714
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Helminth)
RN  - 0 (Antigens, Helminth)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-5)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Vaccines)
RN  - 207137-56-2 (Interleukin-4)
RN  - 9012-63-9 (Cholera Toxin)
SB  - IM
MH  - Adjuvants, Immunologic
MH  - Animals
MH  - Antibodies, Helminth/*blood
MH  - Antigens, Helminth/immunology/*therapeutic use
MH  - Ascariasis/*prevention & control
MH  - Ascaris suum
MH  - Cholera Toxin/immunology
MH  - Female
MH  - Immunoglobulin G/blood
MH  - Interleukin-4/immunology
MH  - Interleukin-5/immunology
MH  - Larva
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Recombinant Proteins/therapeutic use
MH  - Saccharomyces cerevisiae
MH  - Sequence Analysis
MH  - Th2 Cells/*immunology
MH  - Vaccination
MH  - Vaccines/*therapeutic use
EDAT- 2017/07/15 06:00
MHDA- 2017/08/02 06:00
CRDT- 2017/07/15 06:00
PHST- 2017/03/15 [received]
PHST- 2017/07/03 [accepted]
PHST- 2017/07/26 [revised]
AID - 10.1371/journal.pntd.0005769 [doi]
AID - PNTD-D-17-00350 [pii]
PST - epublish
SO  - PLoS Negl Trop Dis. 2017 Jul 14;11(7):e0005769. doi:
      10.1371/journal.pntd.0005769. eCollection 2017 Jul.