Antigenic variation in Trypanosoma brucei infections: an holistic view

1999 ◽  
Vol 112 (19) ◽  
pp. 3187-3192
Author(s):  
C.M. Turner
Keyword(s):  
Immune Responses ◽  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
High Rate ◽  
T Helper 1 ◽  
Holistic View ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Variable Antigen

Trypanosoma brucei parasites undergo clonal phenotypic (antigenic) variation to promote their transmission between mammals and tsetse-fly vectors. This process is classically considered to be a mechanism for evading humoral immune responses, but such an explanation cannot account for the high rate of switching between variable antigens or for their hierarchical (i.e. non-random) expression. I suggest that these anomalies can be explained by a new model: that antigenic variation has evolved as a bifunctional, rather than as a unifunctional, strategy that not only evades humoral immune responses but also enables competition between parasite strains in concomitantly infected hosts. This competition causes a depression of cellular responses. My proposal gives rise to a number of testable predictions. First, low numbers of trypanosomes should express some variable antigen types (VATs) in infections several weeks before these VATs are detectable. Second, as an infection progresses, the number of VATs expressed simultaneously in the population should decrease. Third, immunisation to generate a T helper 1 response against those VATs that are expressed most frequently should lower parasitaemias and reduce virulence.

Trypanosome sociology and antigenic variation

Parasitology ◽  
1989 ◽  
Vol 99 (S1) ◽  
pp. S37-S47 ◽  
Author(s):  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Growth Characteristics ◽  
Tsetse Fly ◽  
Antigenic Specificity ◽  
Surface Coat ◽  
Humoral Immune ◽  
Variable Antigen ◽  
Minority Variants ◽  
Stimulation Of

SUMMARYSurvival of the trypanosome (Trypanosoma brucei) population in the mammalian body depends upon paced stimulation of the host's humoral immune response by different antigenic variants and serial sacrifice of the dominant variant (homotype) so that minority variants (heterotypes) can continue the infection and each become a homotype in its turn. New variants are generated by a spontaneous switch in gene expression so that the trypanosome puts on a surface coat of a glycoprotein differing in antigenic specificity from its predecessor. Homotypes appear in a characteristic order for a given trypanosome clone but what determines this order and the pacing of homotype generation so that the trypanosome does not quickly exhaust its repertoire of variable antigens, is not clear. The tendency of some genes to be expressed more frequently than others may reflect the location within the genome and mode of expression of the genes concerned and may influence homotype succession. Differences in the doubling time of different variants or in the rate at which trypanosomes belonging to a particular variant differentiate into non-dividing (vector infective) stumpy forms have also been invoked to explain how a heterotype's growth characteristics may determine when it becomes a homotype. Recent estimations of the frequency of variable antigen switching in trypanosome populations after transmission through the tsetse fly vector, however, suggest a much higher figure (0·97–2·2 × 10−3switches per cell per generation) than that obtained for syringe-passed infections (10−5–10−7switches per cell per generation) and it seems probable that most of the variable antigen genes are expressed as minority variable antigen types very early in the infection. Instability of expression is a feature of trypanosome clones derived from infective tsetse salivary gland (metacyclic) trypanosomes and it is suggested that high switching rates in tsetse-transmitted infections may delay the growth of certain variants to homotype status until later in the infection.

scholarly journals Chimeric Plant Virus Particles Administered Nasally or Orally Induce Systemic and Mucosal Immune Responses in Mice

1999 ◽  
Vol 73 (2) ◽  
pp. 930-938 ◽  
Author(s):  
Frank R. Brennan ◽  
Trevor Bellaby ◽  
Sharon M. Helliwell ◽  
Tim D. Jones ◽  
Søren Kamstrup ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plant Virus ◽  
Oral Immunization ◽  
Plant Viruses ◽  
T Helper 1 ◽  
Virus Particles ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Recombinant Plant ◽  
Chimeric Plant

ABSTRACT The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone or in the presence of ISCOM matrix, primed CPMV-specific T cells and generated high titers of CPMV- and FnBP-specific immunoglobulin G (IgG) in sera. Furthermore, CPMV- and FnBP-specific IgA and IgG could also be detected in the bronchial, intestinal, and vaginal lavage fluids, highlighting the ability of CVPs to generate antibody at distant mucosal sites. IgG2a and IgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs also generated CPMV- and FnBP-specific serum IgG; however, these titers were significantly lower and more variable than those generated by the intranasal route, and FnBP-specific intestinal IgA was undetectable. Neither the ISCOM matrix nor cholera toxin enhanced these responses. These studies demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.

scholarly journals Control of Giardiasis by Interleukin-17 in Humans and Mice—Are the Questions All Answered?

2015 ◽  
Vol 23 (1) ◽  
pp. 2-5 ◽  
Author(s):  
Steven M. Singer
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Giardia Lamblia ◽  
Antigenic Variation ◽  
Interleukin 17 ◽  
Content Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Key Factor

ABSTRACTFor years, studies of the immune response toGiardia lambliainfection focused on the production of IgA by infected hosts and antigenic variation by the parasite to escape destruction by this IgA. A new study by Hanevik and colleagues (C. S. Saghaug, S. Sørnes, D. Peirasmaki, S. Svärd, N. Langeland, and K. Hanevik, Clin Vaccine Immunol 23:11–18, 2016,http://dx.doi.org/10.1128/CVI.00419-15) highlights the emerging role of interleukin-17 (IL-17) in immunity to this parasite. Along with recent studies ofGiardiainfections of animals, this work shows that IL-17 appears to be essential for the control of these infections and to be a key factor linking cellular and humoral immune responses.

scholarly journals Structure-guided molecular grafting of a complex broadly neutralizing viral epitope

2019 ◽  
Author(s):  
Goran Bajic ◽  
Max J. Maron ◽  
Ming Tian ◽  
Garnett Kelsoe ◽  
Masayuki Kuraoka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigenic Variation ◽  
Viral Evolution ◽  
Molecular Scaffolds ◽  
Receptor Binding Site ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Viral Epitope ◽  
Viral Hemagglutinin ◽  
Universal Influenza Vaccine

ABSTRACTAntigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a “universal” influenza vaccine will come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use non-circulating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These “resurfaced” HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can enrich for RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope.

scholarly journals A lymph node–targeted Amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2

2021 ◽  
Vol 7 (6) ◽  
pp. eabe5819
Author(s):  
Martin P. Steinbuck ◽  
Lochana M. Seenappa ◽  
Aniela Jakubowski ◽  
Lisa K. McNeil ◽  
Christopher M. Haqq ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Lung Parenchyma ◽  
Antibody Responses ◽  
Protein Subunit ◽  
T Helper 1 ◽  
Humoral Immune ◽  
Adaptive Immune ◽  
Humoral Immune Responses ◽  
Cellular And Humoral Immunity

The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid–modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (TH1) cytokines and trafficked into lung parenchyma. Antibody responses favored TH1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

Parasite development and host responses during the establishment of Trypanosoma brucei infection transmitted by tsetse fly

Parasitology ◽  
1984 ◽  
Vol 88 (1) ◽  
pp. 67-84 ◽  
Author(s):  
J. D. Barry ◽  
D. L. Emery
Keyword(s):  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
Host Responses ◽  
Parasite Development ◽  
Large Mammals ◽  
Local Skin ◽  
Sequence Of Events ◽  
Draining Lymph Node ◽  
Variable Antigen

SUMMARYFollowing inoculation of Trypanosoma brucei into large mammals by the tsetse fly a local skin reaction, the ‘chancre’, develops due to trypanosome proliferation. We have cannulated the afferent and efferent lymphatics of the draining lymph node in goats and examined the onset of a cellular reaction, the emigration of the parasite from the chancre and the development of both antigenic variation and the specific immune response. The chancre first became detectable by day 3 post-infection, peaked by day 6 and then subsided. Lymphocyte output increased 6- to 8-fold by day 10 and the number of lymphoblasts increased 50-fold in this period. Both then declined. Trypanosomes were detected in lymph 1–2 days before the chancre, peaked by days 5–6, declined during development of the chancre and then peaked again. The bloodstream population appeared by days 4–5 and displayed different kinetics from that in lymph. Recirculation of parasites through the lymphatics ensued. Lymph-borne trypanosome populations were highly pleomorphic. Parasites in lymph expressed firstly a mixture of the Variable Antigen Types (VATs) which are found characteristically in the tsetse fly, this being followed by a mixture of other VATs. The two groups overlapped in appearance. In the bloodstream the same sequence of events occurred although 2 or 3 days later. The specific antibody response, as measured by radioimmunoassay and agglutination, arose within a few days of the first detection of each VAT. Activities appeared first in the lymph and then in plasma.

scholarly journals Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

2009 ◽  
Vol 5 (4) ◽  
pp. e1000373 ◽  
Author(s):  
Christiane Stahl-Hennig ◽  
Martin Eisenblätter ◽  
Edith Jasny ◽  
Tamara Rzehak ◽  
Klara Tenner-Racz ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Immune Responses ◽  
Rhesus Macaques ◽  
T Helper ◽  
T Helper 1 ◽  
Humoral Immune ◽  
Humoral Immune Responses

Specific humoral immune responses in 12 cases of food sensitization to sesame seed

1997 ◽  
Vol 27 (11) ◽  
pp. 1285-1291 ◽  
Author(s):  
M. N. KOLOPP-SARDA ◽  
D. A. MONERET-VAUTRIN ◽  
B. GOBERT ◽  
G. KANNY ◽  
M. BRODSCHII ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sesame Seed ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Food Sensitization
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