DNA Immunization with the Cysteine-Rich Interdomain Region 1 of the Plasmodium falciparum Variant Antigen Elicits Limited Cross-Reactive Antibody Responses

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Published inInfection and Immunity Vol. 71; no. 8; pp. 4536 - 4543
Main Authors BARUCH, Dror I, GAMAIN, Benoit, MILLER, Louis H
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.08.2003
Subjects
Animals
Antibodies, Protozoan - biosynthesis
Antigens, Protozoan - chemistry
Antigens, Protozoan - genetics
Biological and medical sciences
CHO Cells
Cricetinae
Cross Reactions
Female
Fundamental and applied biological sciences. Psychology
Fungal and Parasitic Infections
Hemagglutination
Malaria Vaccines - genetics
Malaria Vaccines - immunology
Malaria Vaccines - pharmacology
Mice
Mice, Inbred BALB C
Microbiology
Plasmids - genetics
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Vaccines, DNA - genetics
Vaccines, DNA - immunology
Vaccines, DNA - pharmacology
Antigen
Protozoa
Plasmodium falciparum
Apicomplexa
Cysteine
Microbiology
Antibody
Genetic vaccine
Immunity
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Abstract Classifications Services IAI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue IAI About IAI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy Connect to IAI IAI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0019-9567 Online ISSN: 1098-5522 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to IAI .asm.org, visit: IAI       
AbstractList The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target. However, these proteins appear to elicit primarily variant-specific antibodies. We tested if naked DNA immunization can elicit more cross-reactive antibody responses and allow simultaneous immunization with several variant constructs. Mice immunized with plasmid DNA expressing variant cysteine-rich interdomain region 1 (CIDR1) domains of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) developed antibodies that were reactive to the corresponding PfEMP1s as measured by an enzyme-linked immunosorbent assay, flow cytometry, and agglutination of parasitized erythrocytes (PEs). We observed some cross-reactive immune responses; for example, sera from mice immunized with one domain agglutinated PEs of various lines and recognized heterologous domains expressed on the surface of Chinese hamster ovary (CHO) cells. We found no significant antigenic competition when animals were immunized with a mixture of plasmids or immunized sequentially with individual constructs. Moreover, mixed or sequential immunizations resulted in greater cross-reactive agglutination responses than immunization with a single domain. Recombinant protein (Sc y179) immunization after priming with DNA (prime-boost regimen) increased antibody titers to the homologous domain substantially but seemed to diminish the cross-reactive responses somewhat. The titer of agglutinating antibodies was previously shown to correlate with protection. Surprisingly, the agglutination titers of sera from DNA immunization were high, similar to those of pooled human hyperimmune sera. These sera also appeared to give limited low-titer variant transcending agglutination. Thus, DNA immunization appears to be a very useful tool for developing variant antigen vaccines.
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ABSTRACT The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target. However, these proteins appear to elicit primarily variant-specific antibodies. We tested if naked DNA immunization can elicit more cross-reactive antibody responses and allow simultaneous immunization with several variant constructs. Mice immunized with plasmid DNA expressing variant cysteine-rich interdomain region 1 (CIDR1) domains of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) developed antibodies that were reactive to the corresponding PfEMP1s as measured by an enzyme-linked immunosorbent assay, flow cytometry, and agglutination of parasitized erythrocytes (PEs). We observed some cross-reactive immune responses; for example, sera from mice immunized with one domain agglutinated PEs of various lines and recognized heterologous domains expressed on the surface of Chinese hamster ovary (CHO) cells. We found no significant antigenic competition when animals were immunized with a mixture of plasmids or immunized sequentially with individual constructs. Moreover, mixed or sequential immunizations resulted in greater cross-reactive agglutination responses than immunization with a single domain. Recombinant protein (Sc y179) immunization after priming with DNA (prime-boost regimen) increased antibody titers to the homologous domain substantially but seemed to diminish the cross-reactive responses somewhat. The titer of agglutinating antibodies was previously shown to correlate with protection. Surprisingly, the agglutination titers of sera from DNA immunization were high, similar to those of pooled human hyperimmune sera. These sera also appeared to give limited low-titer variant transcending agglutination. Thus, DNA immunization appears to be a very useful tool for developing variant antigen vaccines.
The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target. However, these proteins appear to elicit primarily variant-specific antibodies. We tested if naked DNA immunization can elicit more cross-reactive antibody responses and allow simultaneous immunization with several variant constructs. Mice immunized with plasmid DNA expressing variant cysteine-rich interdomain region 1 (CIDR1) domains of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) developed antibodies that were reactive to the corresponding PfEMP1s as measured by an enzyme-linked immunosorbent assay, flow cytometry, and agglutination of parasitized erythrocytes (PEs). We observed some cross-reactive immune responses; for example, sera from mice immunized with one domain agglutinated PEs of various lines and recognized heterologous domains expressed on the surface of Chinese hamster ovary (CHO) cells. We found no significant antigenic competition when animals were immunized with a mixture of plasmids or immunized sequentially with individual constructs. Moreover, mixed or sequential immunizations resulted in greater cross-reactive agglutination responses than immunization with a single domain. Recombinant protein (Sc y179) immunization after priming with DNA (prime-boost regimen) increased antibody titers to the homologous domain substantially but seemed to diminish the cross-reactive responses somewhat. The titer of agglutinating antibodies was previously shown to correlate with protection. Surprisingly, the agglutination titers of sera from DNA immunization were high, similar to those of pooled human hyperimmune sera. These sera also appeared to give limited low-titer variant transcending agglutination. Thus, DNA immunization appears to be a very useful tool for developing variant antigen vaccines.
Author Louis H. Miller
Benoit Gamain
Dror I. Baruch
AuthorAffiliation Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Issue 8
Keywords Antigen
Protozoa
Plasmodium falciparum
Apicomplexa
Cysteine
Microbiology
Antibody
Genetic vaccine
Immunity
Language English
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Corresponding author. Mailing address: Laboratory of Malaria and Vector Research, NIAID, NIH, Bldg. 4, Room B1-37, 4 Center Drive MSC 0425, Bethesda, MD 20892-0425. Phone: (301) 451-4945. Fax: (301) 402-0079. E-mail: dbaruch@niaid.nih.gov.
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Snippet Classifications Services IAI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit...
The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target. However, these...
ABSTRACT The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target....
The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target. However, these...
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SubjectTerms Animals
Antibodies, Protozoan - biosynthesis
Antigens, Protozoan - chemistry
Antigens, Protozoan - genetics
Biological and medical sciences
CHO Cells
Cricetinae
Cross Reactions
Female
Fundamental and applied biological sciences. Psychology
Fungal and Parasitic Infections
Hemagglutination
Malaria Vaccines - genetics
Malaria Vaccines - immunology
Malaria Vaccines - pharmacology
Mice
Mice, Inbred BALB C
Microbiology
Plasmids - genetics
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Vaccines, DNA - genetics
Vaccines, DNA - immunology
Vaccines, DNA - pharmacology
Title DNA Immunization with the Cysteine-Rich Interdomain Region 1 of the Plasmodium falciparum Variant Antigen Elicits Limited Cross-Reactive Antibody Responses
URI http://iai.asm.org/content/71/8/4536.abstract
https://www.ncbi.nlm.nih.gov/pubmed/12874333
https://search.proquest.com/docview/18796917
https://search.proquest.com/docview/73506503
https://pubmed.ncbi.nlm.nih.gov/PMC166004
Volume 71
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