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Marina N. Matos, Silvia I. Cazorla, Kai Schulze, Thomas Ebensen, Carlos A. Guzmán, Emilio L. Malchiodi
Immunization with Tc52 or its amino terminal domain adjuvanted with c-di-AMP induces Th17+Th1 specific immune responses and confers protection against Trypanosoma cruzi
www.plosntds.org
www.plosntds.org
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3.1918 0 Td
(candidate)Tj
4.1045 0 Td
(against)Tj
/F13 1 Tf
3.0274 0 Td
[()]TJ
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(.)Tj
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1.0375 0 Td
[(\n)1()-9(\r)]TJ
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(this)Tj
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([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
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1.7404 0 Td
(17)Tj
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4.184 0 Td
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1.61 0 Td
(demon-)Tj
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1.7801 0 Td
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(gives)Tj
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2.5399 0 Td
(protection)Tj
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(than)Tj
2.0296 0 Td
(CTc52)Tj
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(and)Tj
1.7292 0 Td
(similar)Tj
2.9877 0 Td
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1.0261 0 Td
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4.388 0 Td
(Tc52)Tj
2.2053 0 Td
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/F8 1 Tf
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([)Tj
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(18)Tj
0 g
(].)Tj
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(then)Tj
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(the)Tj
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([)Tj
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0 g
(].)Tj
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(20)Tj
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3.0784 0 Td
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(protein)Tj
3.1521 0 Td
(Tc52)Tj
2.2053 0 Td
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/F13 1 Tf
-35.3081 -1.2983 Td
[()2(\r)4(\n)13()18(\r)4()]TJ
2.6645 0 Td
[()4()9()11()11()-9(\r)-4()]TJ
/F8 1 Tf
(,)Tj
3.4582 0 Td
(an)Tj
1.2019 0 Td
(organism)Tj
3.9969 0 Td
(with)Tj
1.9955 0 Td
(GRAS)Tj
2.7156 0 Td
(\(Generally)Tj
4.4277 0 Td
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4.8359 0 Td
(As)Tj
1.2699 0 Td
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2.177 0 Td
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(USA)Tj
2.1146 0 Td
(FDA)Tj
2.1713 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
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(,)Tj
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1.7348 0 Td
(22)Tj
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(].)Tj
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(infection)Tj
3.7927 0 Td
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1.1849 0 Td
[()]TJ
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(.)Tj
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1.0318 0 Td
[(\n)1()-9(\r)]TJ
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2.16 0 Td
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(vector-mediated)Tj
6.7691 0 Td
(breaks)Tj
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1.8936 0 Td
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(mucosa,)Tj
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(and)Tj
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(organ)Tj
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(transplants,)Tj
4.8643 0 Td
(by)Tj
1.1792 0 Td
(congenital)Tj
4.3823 0 Td
(infection)Tj
3.7927 0 Td
(and)Tj
1.7292 0 Td
(by)Tj
1.1848 0 Td
(oral)Tj
1.7745 0 Td
(route)Tj
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(through)Tj
3.4469 0 Td
(the)Tj
-35.2514 -1.2983 Td
(gastrointestinal)Tj
6.3495 0 Td
(tract)Tj
2.0466 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(],)Tj
2.075 0 Td
(we)Tj
1.3266 0 Td
(analyzed)Tj
3.702 0 Td
(vaccine)Tj
3.1975 0 Td
(candidates)Tj
4.4617 0 Td
(that)Tj
1.7801 0 Td
(induce)Tj
2.9367 0 Td
(both)Tj
2.0579 0 Td
(systemic)Tj
3.634 0 Td
(and)Tj
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(mucosal)Tj
3.5376 0 Td
(immunity.)Tj
4.4503 0 Td
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1.7802 0 Td
(novel)Tj
2.3981 0 Td
(mucosal)Tj
3.5433 0 Td
(adjuvant)Tj
3.702 0 Td
(bis-\(3',5'\)-cyclic)Tj
6.5763 0 Td
(dimeric)Tj
3.3222 0 Td
(adenosine)Tj
4.2633 0 Td
(mono-)Tj
-33.5733 -1.2983 Td
(phosphate)Tj
4.3313 0 Td
(\(c-di-AMP\))Tj
4.9549 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(bacterial)Tj
3.6284 0 Td
(second)Tj
3.0103 0 Td
(messenger,)Tj
4.6432 0 Td
(involved)Tj
3.6453 0 Td
(in)Tj
1.0375 0 Td
(sensing)Tj
3.1974 0 Td
(DNA)Tj
2.3754 0 Td
(integrity,)Tj
-32.326 -1.2983 Td
(control)Tj
3.118 0 Td
(of)Tj
1.0148 0 Td
(cell)Tj
1.5648 0 Td
(wall)Tj
1.8255 0 Td
(and)Tj
1.7347 0 Td
(potassium)Tj
4.3087 0 Td
(homeostasis)Tj
5.091 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
2.0749 0 Td
(This)Tj
1.9843 0 Td
(compound)Tj
4.6034 0 Td
(promotes)Tj
4.0252 0 Td
(expression)Tj
4.4617 0 Td
(of)Tj
-35.807 -1.3039 Td
(type)Tj
1.9105 0 Td
(I)Tj
0.5612 0 Td
(IFN)Tj
1.8255 0 Td
(and)Tj
1.7292 0 Td
(TNF)Tj
2.0976 0 Td
(through)Tj
3.4412 0 Td
(the)Tj
1.474 0 Td
(activation)Tj
4.1499 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(STING/TBK1)Tj
5.7713 0 Td
(axis.)Tj
1.9729 0 Td
(The)Tj
1.7801 0 Td
(co-administration)Tj
7.4494 0 Td
(of)Tj
-35.8296 -1.2982 Td
(an)Tj
1.2018 0 Td
(antigen)Tj
3.2032 0 Td
(and)Tj
1.7291 0 Td
(c-di-AMP)Tj
4.2803 0 Td
(by)Tj
1.1792 0 Td
(intranasal)Tj
4.1612 0 Td
(route)Tj
2.3471 0 Td
(in)Tj
1.0375 0 Td
(BALB/c)Tj
3.3562 0 Td
(mice)Tj
2.1543 0 Td
(induced)Tj
3.4639 0 Td
(both)Tj
2.0636 0 Td
(systemic)Tj
3.6283 0 Td
(and)Tj
-33.8057 -1.2983 Td
(mucosal)Tj
3.5376 0 Td
(antibody)Tj
3.7644 0 Td
(responses,)Tj
4.3199 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.652 0 Td
(balanced)Tj
3.7644 0 Td
(Th1/Th2/Th17)Tj
6.2022 0 Td
(cellular)Tj
3.1351 0 Td
(specific)Tj
3.1918 0 Td
(immunity)Tj
4.2235 0 Td
(pattern)Tj
-34.52 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
2.0749 0 Td
(Another)Tj
3.583 0 Td
(mucosal)Tj
3.5376 0 Td
(adjuvant,)Tj
3.9288 0 Td
(a)Tj
0.6519 0 Td
(pegylated)Tj
4.0082 0 Td
(derivate)Tj
3.4242 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
/F14 1 Tf
1.4684 0 Td
()Tj
/F8 1 Tf
(-galactosyl-ceramide)Tj
9.0481 0 Td
(\()Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(GC-)Tj
-32.7399 -1.2983 Td
(PEG\),)Tj
2.6305 0 Td
(induces)Tj
3.2938 0 Td
(a)Tj
0.6577 0 Td
(dominant)Tj
4.1725 0 Td
(Th2)Tj
1.8312 0 Td
(immune)Tj
3.6283 0 Td
(response)Tj
3.7304 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(],)Tj
2.0806 0 Td
(and)Tj
1.7291 0 Td
(more)Tj
2.3414 0 Td
(interestingly,)Tj
5.4198 0 Td
(it)Tj
0.7824 0 Td
(inhibits)Tj
-32.2977 -1.2983 Td
(Th17)Tj
2.3073 0 Td
(cell)Tj
1.5591 0 Td
(differentiation)Tj
5.981 0 Td
(by)Tj
1.1793 0 Td
(activating)Tj
4.1102 0 Td
(NKT)Tj
2.245 0 Td
(cells)Tj
1.9162 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(].)Tj
2.0806 0 Td
(The)Tj
1.7802 0 Td
(role)Tj
1.7688 0 Td
(of)Tj
1.0148 0 Td
(IL-17)Tj
2.3981 0 Td
(and)Tj
1.7348 0 Td
(Th17)Tj
2.3073 0 Td
(cells)Tj
1.9219 0 Td
(in)Tj
/F13 1 Tf
-34.3046 -1.2982 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
1.0318 0 Td
[(\n)1()-9(\r)]TJ
/F8 1 Tf
2.1599 0 Td
(infection)Tj
3.7928 0 Td
(are)Tj
1.4513 0 Td
(still)Tj
1.6384 0 Td
(not)Tj
1.5761 0 Td
(well)Tj
1.8198 0 Td
(characterized.)Tj
5.7826 0 Td
(Though,)Tj
3.6114 0 Td
(reports)Tj
3.067 0 Td
(suggested)Tj
4.0762 0 Td
(that)Tj
1.7802 0 Td
(IL-17)Tj
2.3981 0 Td
(could)Tj
-34.1856 -1.3039 Td
(have)Tj
2.0579 0 Td
(a)Tj
0.652 0 Td
(protective)Tj
4.2065 0 Td
(role)Tj
1.7688 0 Td
(in)Tj
1.0375 0 Td
(infection)Tj
3.7871 0 Td
(and)Tj
1.7348 0 Td
(tissue)Tj
2.4548 0 Td
(damage)Tj
3.3278 0 Td
(control)Tj
3.1181 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(].)Tj
3.549 0 Td
(In)Tj
1.1055 0 Td
(this)Tj
1.6781 0 Td
(work)Tj
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(we)Tj
1.3266 0 Td
(use)Tj
-34.0835 -1.2983 Td
(c-di-AMP)Tj
4.2746 0 Td
(as)Tj
1.0148 0 Td
(an)Tj
1.2018 0 Td
(adjuvant)Tj
3.7021 0 Td
(for)Tj
1.3833 0 Td
(intranasal)Tj
4.1669 0 Td
(immunization)Tj
5.9357 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.474 0 Td
(recombinant)Tj
5.3688 0 Td
(proteins)Tj
3.5092 0 Td
(Tc52,)Tj
-34.0268 -1.2983 Td
(NTc52)Tj
2.9423 0 Td
(and)Tj
1.7291 0 Td
(CTc52.)Tj
3.0954 0 Td
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(we)Tj
1.3266 0 Td
(test)Tj
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(the)Tj
1.4683 0 Td
(co-administration)Tj
7.4551 0 Td
(of)Tj
1.0148 0 Td
(NTc52)Tj
2.9423 0 Td
(together)Tj
3.532 0 Td
(with)Tj
1.9956 0 Td
(c-di-AMP)Tj
4.2746 0 Td
(and)Tj
/F14 1 Tf
-35.6199 -1.3039 Td
()Tj
/F8 1 Tf
(GC-PEG)Tj
4.3596 0 Td
(to)Tj
1.0261 0 Td
(evaluate)Tj
3.464 0 Td
(the)Tj
1.4683 0 Td
(ability)Tj
2.6929 0 Td
(of)Tj
/F14 1 Tf
1.0148 0 Td
()Tj
/F8 1 Tf
(GC-PEG)Tj
4.3653 0 Td
(to)Tj
1.0262 0 Td
(block)Tj
2.398 0 Td
(Th17)Tj
2.3074 0 Td
(response)Tj
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(and)Tj
1.7291 0 Td
(its)Tj
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(effect)Tj
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(in)Tj
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(the)Tj
1.4684 0 Td
(con-)Tj
-35.6029 -1.2982 Td
(ferred)Tj
2.6248 0 Td
(protection)Tj
4.3823 0 Td
(against)Tj
/F13 1 Tf
3.0274 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
1.0375 0 Td
[(\n)1()-9(\r)]TJ
/F8 1 Tf
2.16 0 Td
(infection.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 265.2094 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.5023 Td
(Parasite)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 230.2299 cm
BT
/F13 1 Tf
1 TL
-0.004 Tc
0 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
1.0318 0 Td
[(\n)1()-9(\r)]TJ
/F8 1 Tf
2.1599 0 Td
(epimastigotes)Tj
5.6636 0 Td
(\(RA)Tj
1.8652 0 Td
(strain\))Tj
2.8403 0 Td
(were)Tj
2.126 0 Td
(grown)Tj
2.7949 0 Td
(in)Tj
1.0375 0 Td
(LIT)Tj
1.7064 0 Td
(medium)Tj
3.6057 0 Td
(as)Tj
1.0148 0 Td
(previously)Tj
4.354 0 Td
(described)Tj
4.0478 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
-34.2479 -1.3039 Td
(The)Tj
/F13 1 Tf
1.7801 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
1.0375 0 Td
[(\n)1()-9(\r)]TJ
/F8 1 Tf
2.16 0 Td
(bloodstream)Tj
5.2213 0 Td
(trypomastigotes)Tj
6.6047 0 Td
(\(RA)Tj
1.8652 0 Td
(strain\))Tj
2.8403 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4684 0 Td
(recombinant)Tj
5.3688 0 Td
(Tulahuen)Tj
4.0705 0 Td
(strain)Tj
-34.1459 -1.2982 Td
(expressing)Tj
/F14 1 Tf
4.422 0 Td
()Tj
/F8 1 Tf
(-galactosidase)Tj
6.2418 0 Td
(\(Tul-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(-Gal\))Tj
4.8642 0 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(])Tj
1.8539 0 Td
(were)Tj
2.1203 0 Td
(isolated)Tj
3.2825 0 Td
(from)Tj
2.211 0 Td
(the)Tj
1.4683 0 Td
(blood)Tj
2.5115 0 Td
(of)Tj
1.0148 0 Td
(infected)Tj
3.4242 0 Td
(mice.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 178.0157 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Tc52,)Tj
2.7023 0 Td
(NTc52)Tj
3.1371 0 Td
(and)Tj
1.8614 0 Td
(CTc52)Tj
3.1418 0 Td
(cloning)Tj
3.3401 0 Td
(and)Tj
1.8615 0 Td
(expression)Tj
4.9984 0 Td
(in)Tj
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(absence)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(antigen.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 665.9149 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Enzyme-Linked)Tj
7.0347 0 Td
(Inmuno)Tj
3.5197 0 Td
(Sorbent)Tj
3.685 0 Td
(SPOT\(ELISPOT\))Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 648.907 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(IFN-)Tj
/F14 1 Tf
(\r)Tj
/F8 1 Tf
(,)Tj
2.8573 0 Td
(IL-4)Tj
1.9218 0 Td
(and)Tj
1.7292 0 Td
(IL-17)Tj
2.4037 0 Td
(producing)Tj
4.371 0 Td
(spleen)Tj
2.7439 0 Td
(cells)Tj
1.9162 0 Td
(in)Tj
1.0375 0 Td
(response)Tj
3.7361 0 Td
(to)Tj
1.0204 0 Td
(antigenic)Tj
3.9005 0 Td
(stimulus)Tj
-33.8511 -1.2982 Td
(was)Tj
1.6951 0 Td
(determined)Tj
4.8528 0 Td
(by)Tj
1.1849 0 Td
(ELISPOT.)Tj
4.286 0 Td
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4.388 0 Td
(well)Tj
1.8198 0 Td
(plates)Tj
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(were)Tj
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(sensitized)Tj
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(with)Tj
1.9956 0 Td
(capture)Tj
3.2145 0 Td
(antibodies)Tj
-32.173 -1.2983 Td
(\(anti-IFN-)Tj
/F14 1 Tf
(\r)Tj
/F8 1 Tf
(,)Tj
5.0909 0 Td
(anti-IL-4,)Tj
4.0479 0 Td
(or)Tj
1.0998 0 Td
(anti-IL-17\))Tj
4.6375 0 Td
(for)Tj
1.3889 0 Td
(16)Tj
1.1679 0 Td
(h,)Tj
0.9751 0 Td
(at)Tj
0.9525 0 Td
(4C,)Tj
1.9785 0 Td
(and)Tj
1.7292 0 Td
(then)Tj
2.0182 0 Td
(blocked)Tj
3.3505 0 Td
(\(with)Tj
2.3358 0 Td
(RPMI)Tj
2.6362 0 Td
(medium)Tj
-33.4089 -1.3039 Td
(supplemented)Tj
5.8506 0 Td
(with)Tj
2.0013 0 Td
(10%)Tj
1.9275 0 Td
(fetal)Tj
1.9106 0 Td
(bovine)Tj
2.9253 0 Td
(serum,)Tj
2.948 0 Td
(FBS\).)Tj
2.3698 0 Td
(Splenocytes)Tj
4.8982 0 Td
(\(2)Tj
1.0375 0 Td
(x)Tj
0.6859 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 475.0866 614.3811 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 480.8125 609.9023 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(or)Tj
1.0998 0 Td
(4)Tj
0.6973 0 Td
(x)Tj
0.6803 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 515.1118 614.3811 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 520.8944 609.9023 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells/well\))Tj
-32.0879 -1.2982 Td
(were)Tj
2.1203 0 Td
(added)Tj
2.6588 0 Td
(in)Tj
1.0375 0 Td
(presence)Tj
3.7134 0 Td
(or)Tj
1.0998 0 Td
(absence)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(Tc52)Tj
2.2053 0 Td
(\(0.5)Tj
/F15 1 Tf
1.7348 0 Td
[()]TJ
/F8 1 Tf
(g/well\),)Tj
3.6907 0 Td
(and)Tj
1.7291 0 Td
(incubated)Tj
4.1783 0 Td
(at)Tj
0.9524 0 Td
(37C,)Tj
2.4491 0 Td
(5%)Tj
1.4569 0 Td
(CO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 547.8803 595.2755 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 551.4519 596.9196 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(,)Tj
0.4478 0 Td
(for)Tj
-35.5915 -1.2982 Td
(24)Tj
1.1679 0 Td
(h)Tj
0.7483 0 Td
(for)Tj
1.389 0 Td
(IFN-)Tj
/F14 1 Tf
(\r)Tj
/F8 1 Tf
2.6305 0 Td
(and)Tj
1.7292 0 Td
(48)Tj
1.1678 0 Td
(h)Tj
0.7484 0 Td
(for)Tj
1.3889 0 Td
(IL-4)Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(IL-17.)Tj
2.6306 0 Td
(Plates)Tj
2.5398 0 Td
(were)Tj
2.1203 0 Td
(washed)Tj
3.1805 0 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0182 0 Td
(incubated)Tj
4.1783 0 Td
(\(2h,)Tj
1.7858 0 Td
(25C\))Tj
-34.8036 -1.3039 Td
(with)Tj
1.9956 0 Td
(biotinylated)Tj
5.0003 0 Td
(detection)Tj
3.9345 0 Td
(antibody)Tj
3.7643 0 Td
(and)Tj
1.7348 0 Td
(then)Tj
2.0183 0 Td
(with)Tj
1.9956 0 Td
(Avidin-HRP.)Tj
5.4935 0 Td
(As)Tj
1.2642 0 Td
(peroxidase)Tj
4.5184 0 Td
(substrate,)Tj
-31.7195 -1.2983 Td
(3-amino-9-ethil-carbazole)Tj
10.6696 0 Td
(\(AEC\))Tj
2.8176 0 Td
(was)Tj
1.7008 0 Td
(used.)Tj
2.2847 0 Td
(Plates)Tj
2.5398 0 Td
(were)Tj
2.126 0 Td
(scanned)Tj
3.4866 0 Td
(and)Tj
1.7291 0 Td
(spots)Tj
2.262 0 Td
(were)Tj
2.126 0 Td
(quantified)Tj
4.3085 0 Td
(in)Tj
-36.0507 -1.2983 Td
(an)Tj
1.2019 0 Td
(ImmunoSpot)Tj
5.5786 0 Td
(CTL.)Tj
2.262 0 Td
(Results)Tj
3.0557 0 Td
(were)Tj
2.126 0 Td
(expressed)Tj
4.0932 0 Td
(as)Tj
1.0148 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(spots)Tj
2.262 0 Td
(for)Tj
1.389 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 483.6472 549.3543 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 489.4299 544.9322 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 516.4157 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Blood)Tj
2.7401 0 Td
(parasite)Tj
3.7323 0 Td
(levels,)Tj
3.019 0 Td
(survival)Tj
3.5669 0 Td
(and)Tj
1.8615 0 Td
(weight)Tj
3.0756 0 Td
(monitoring)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 499.4645 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Twenty)Tj
3.2371 0 Td
(days)Tj
2.0012 0 Td
(after)Tj
2.0353 0 Td
(the)Tj
1.4683 0 Td
(last)Tj
1.5591 0 Td
(immunization,)Tj
6.1625 0 Td
(mice)Tj
2.1543 0 Td
(were)Tj
2.1203 0 Td
(infected)Tj
3.4242 0 Td
(by)Tj
1.1792 0 Td
(intraperitoneal)Tj
6.1795 0 Td
(route)Tj
2.3471 0 Td
(with)Tj
-33.8681 -1.3039 Td
(1000)Tj
/F13 1 Tf
2.1203 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
1.0374 0 Td
[(\n)1()-9(\r)]TJ
/F8 1 Tf
2.16 0 Td
(bloodstream)Tj
5.2214 0 Td
(trypomastigotes)Tj
6.6047 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(highly)Tj
2.7099 0 Td
(virulent)Tj
3.3562 0 Td
(RA)Tj
1.525 0 Td
(strain.)Tj
2.727 0 Td
(Weight)Tj
3.1691 0 Td
(and)Tj
1.7291 0 Td
(parasi-)Tj
-34.8432 -1.2982 Td
(temia)Tj
2.4604 0 Td
(were)Tj
2.126 0 Td
(measured)Tj
4.1045 0 Td
(every)Tj
2.3471 0 Td
(2)Tj
0.6973 0 Td
(or)Tj
1.0998 0 Td
(3)Tj
0.6917 0 Td
(days)Tj
2.0012 0 Td
(after)Tj
2.0353 0 Td
(the)Tj
1.4683 0 Td
(challenge)Tj
3.9572 0 Td
(as)Tj
1.0148 0 Td
(reported)Tj
3.6623 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].The)Tj
3.6397 0 Td
(change)Tj
3.0387 0 Td
(in)Tj
-34.3443 -1.2983 Td
(weight)Tj
2.8856 0 Td
(was)Tj
1.7008 0 Td
(expressed)Tj
4.0932 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(percentage)Tj
4.5468 0 Td
(\(W%\))Tj
2.6248 0 Td
(and)Tj
1.7292 0 Td
(calculated)Tj
4.2066 0 Td
(as)Tj
1.0148 0 Td
(follows:)Tj
3.2825 0 Td
(W%)Tj
1.9445 0 Td
(=)Tj
0.7994 0 Td
(\(WiWo\))Tj
4.5297 0 Td
(x)Tj
-35.0246 -1.3039 Td
(100%/Wo,)Tj
4.4276 0 Td
(where)Tj
2.6533 0 Td
(Wo)Tj
1.6894 0 Td
(is)Tj
0.8504 0 Td
(the)Tj
1.4683 0 Td
(weight)Tj
2.8857 0 Td
(of)Tj
1.0148 0 Td
(each)Tj
2.0296 0 Td
(mouse)Tj
2.8573 0 Td
(immediately)Tj
5.2043 0 Td
(before)Tj
2.7383 0 Td
(infection,)Tj
4.0195 0 Td
(and)Tj
1.7291 0 Td
(Wi)Tj
1.4513 0 Td
(is)Tj
0.8504 0 Td
(its)Tj
-35.8693 -1.2983 Td
(weight)Tj
2.8856 0 Td
(at)Tj
0.9524 0 Td
(day)Tj
1.6328 0 Td
(i)Tj
0.4875 0 Td
(post-infection.)Tj
6.0548 0 Td
(Survival)Tj
3.4526 0 Td
(was)Tj
1.6951 0 Td
(monitored)Tj
4.49 0 Td
(daily.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 405.9779 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Statistical)Tj
4.4504 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 388.97 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Statistical)Tj
4.0195 0 Td
(analyses)Tj
3.4865 0 Td
(were)Tj
2.1203 0 Td
(carried)Tj
3.0388 0 Td
(out)Tj
1.5533 0 Td
(with)Tj
1.9956 0 Td
(Prism)Tj
2.6022 0 Td
(software)Tj
3.583 0 Td
(version)Tj
3.1578 0 Td
(5.0)Tj
1.3946 0 Td
(\(GraphPad,)Tj
4.8699 0 Td
(San)Tj
1.6781 0 Td
(Diego,)Tj
-33.4996 -1.2982 Td
(CA\),)Tj
2.1316 0 Td
(and)Tj
1.7291 0 Td
(R)Tj
0.8447 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(];)Tj
2.075 0 Td
(using)Tj
2.3867 0 Td
(a)Tj
0.6577 0 Td
(nonparametric)Tj
6.1851 0 Td
(Kruskal-Wallis)Tj
6.1965 0 Td
(test)Tj
1.6044 0 Td
(and)Tj
1.7291 0 Td
(Dunn's)Tj
3.1578 0 Td
(posttest.)Tj
3.5093 0 Td
(The)Tj
1.7801 0 Td
(survival)Tj
-33.9871 -1.3039 Td
(curves)Tj
2.7779 0 Td
(were)Tj
2.126 0 Td
(analyzed)Tj
3.702 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.6519 0 Td
(log)Tj
1.44 0 Td
(rank)Tj
2.0693 0 Td
(Mantel-Cox)Tj
5.0513 0 Td
(test.)Tj
1.8255 0 Td
(All)Tj
1.4003 0 Td
(the)Tj
1.4683 0 Td
(comparisons)Tj
5.3348 0 Td
(were)Tj
2.126 0 Td
(done)Tj
2.2223 0 Td
(in)Tj
1.0375 0 Td
(refer-)Tj
-35.2287 -1.2983 Td
(ence)Tj
2.0352 0 Td
(to)Tj
1.0261 0 Td
(control)Tj
3.1238 0 Td
(groups)Tj
2.9707 0 Td
(\(PBS,)Tj
2.3981 0 Td
(c-di-AMP)Tj
4.2746 0 Td
(or)Tj
/F14 1 Tf
1.0998 0 Td
()Tj
/F8 1 Tf
(GC-PEG\),)Tj
4.9266 0 Td
(except)Tj
2.7723 0 Td
(when)Tj
2.4038 0 Td
(indicated.)Tj
4.1612 0 Td
(P)Tj
0.7824 0 Td
(values)Tj
2.6645 0 Td
(of)Tj
1.0148 0 Td
(less)Tj
-35.6539 -1.2983 Td
(than)Tj
2.0295 0 Td
(0.05)Tj
1.8709 0 Td
(were)Tj
2.1203 0 Td
(considered)Tj
4.6034 0 Td
(significant.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 308.4661 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
/F0 1 Tf
0 -1.4976 Td
(All)Tj
1.3133 0 Td
(tested)Tj
2.915 0 Td
(adjuvants)Tj
4.4457 0 Td
(enhance)Tj
4.0064 0 Td
(systemic)Tj
4.0772 0 Td
(antigen-specific)Tj
7.0772 0 Td
(antibody)Tj
-23.8348 -1.1669 Td
(response)Tj
4.2803 0 Td
(in)Tj
0.9874 0 Td
(vaccinated)Tj
4.9418 0 Td
(mice)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 259.4834 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(antigen)Tj
3.2088 0 Td
(specific)Tj
3.1861 0 Td
(antibody)Tj
3.7644 0 Td
(responses)Tj
4.0989 0 Td
(developed)Tj
4.2689 0 Td
(after)Tj
2.0353 0 Td
(immunization)Tj
5.9357 0 Td
(were)Tj
2.126 0 Td
(analyzed)Tj
3.702 0 Td
(by)Tj
-34.1062 -1.2982 Td
(ELISA)Tj
2.8289 0 Td
(in)Tj
1.0318 0 Td
(sera)Tj
1.8085 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1509 0 Td
(mice)Tj
2.1543 0 Td
(immunized.)Tj
5.057 0 Td
(Plates)Tj
2.5398 0 Td
(were)Tj
2.126 0 Td
(sensitized)Tj
4.1102 0 Td
(with)Tj
1.9955 0 Td
(full-length)Tj
4.388 0 Td
(Tc52)Tj
2.2054 0 Td
(instead)Tj
3.0841 0 Td
(of)Tj
-35.4952 -1.3039 Td
(the)Tj
1.4683 0 Td
(immunizing)Tj
5.1647 0 Td
(antigen)Tj
3.2031 0 Td
(\(Tc52,)Tj
2.7723 0 Td
(NTc52)Tj
2.9423 0 Td
(or)Tj
1.0999 0 Td
(CTc52\),)Tj
3.4355 0 Td
(to)Tj
1.0205 0 Td
(evaluate)Tj
3.4639 0 Td
(the)Tj
1.4683 0 Td
(elicited)Tj
3.1011 0 Td
(antibodies)Tj
4.3597 0 Td
(that)Tj
1.7801 0 Td
(rec-)Tj
-35.2797 -1.2983 Td
(ognize)Tj
2.8402 0 Td
(their)Tj
2.109 0 Td
(cognate)Tj
3.3222 0 Td
(epitope)Tj
3.1748 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(molecule)Tj
3.8381 0 Td
(exposed)Tj
3.4412 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(parasite.)Tj
3.549 0 Td
(Mice)Tj
2.228 0 Td
(immunized)Tj
4.8359 0 Td
(with)Tj
-34.4974 -1.2983 Td
(recombinant)Tj
5.3687 0 Td
(proteins)Tj
3.515 0 Td
(\(Tc52,)Tj
2.7666 0 Td
(NTc52)Tj
2.9423 0 Td
(and)Tj
1.7348 0 Td
(CTc52\))Tj
3.2088 0 Td
(plus)Tj
1.8709 0 Td
(c-di-AMP,)Tj
4.5013 0 Td
(and)Tj
1.7292 0 Td
(those)Tj
2.3357 0 Td
(immunized)Tj
4.8359 0 Td
(with)Tj
-34.8092 -1.3039 Td
(NTc52)Tj
2.9423 0 Td
(plus)Tj
1.8708 0 Td
(c-di-AMP+)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(GC-PEG)Tj
8.9972 0 Td
(or)Tj
1.0998 0 Td
(ODN-CpG,)Tj
4.9096 0 Td
(developed)Tj
4.2689 0 Td
(high)Tj
2.0126 0 Td
(titers)Tj
2.2394 0 Td
(of)Tj
1.0148 0 Td
(Tc52-specific)Tj
5.5275 0 Td
(IgG)Tj
-34.8829 -1.2982 Td
(antibodies)Tj
4.3596 0 Td
(with)Tj
1.9956 0 Td
(significant)Tj
4.388 0 Td
(differences)Tj
4.5694 0 Td
(compared)Tj
4.2406 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(control)Tj
3.1237 0 Td
(group.)Tj
2.8347 0 Td
(Mice)Tj
2.228 0 Td
(immunized)Tj
4.8302 0 Td
(just)Tj
-35.0643 -1.2983 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.4684 0 Td
(proteins)Tj
3.5149 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(absence)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(any)Tj
1.6611 0 Td
(adjuvant)Tj
3.702 0 Td
(did)Tj
1.5421 0 Td
(not)Tj
1.5703 0 Td
(show)Tj
2.3018 0 Td
(antibodies)Tj
4.3596 0 Td
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