%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Ivana Soria, Valeria Quattrocchi, Cecilia Langellotti, Mariela Gammella, Sebastian Digiacomo, Beatriz Garcia de la Torre, David Andreu, Maria Montoya, Francisco Sobrino, Esther Blanco, Patricia Zamorano
Dendrimeric peptides can confer protection against foot-and-mouth disease virus in cattle
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 12 0 R/Contents 13 0 R/TrimBox[0 0 612 792]>>
endobj
12 0 obj
[14 0 R 15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R]
endobj
14 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref001)>>
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref001)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref002)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref004)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref005)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref006)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref005)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref007)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref008)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref009)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref010)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref003)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref004)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref011)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.g001)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref011)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref012)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref004)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0185184.ref013)>>
endobj
34 0 obj
<>/Border[0 0 0]/A 35 0 R>>
endobj
35 0 obj
<>
endobj
13 0 obj
[36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R]
endobj
36 0 obj
<>stream
q
0.83 0.64 0.02 0 k
226.3181 693.2976 m
231.0236 693.2976 l
h
f*
513.5811 602.3055 m
518.3433 602.3055 l
h
f*
238.9606 576.3402 m
243.7228 576.3402 l
h
f*
228.4157 537.3354 m
233.178 537.3354 l
h
f*
237.6567 537.3354 m
242.4189 537.3354 l
h
f*
376.0441 498.3307 m
380.8063 498.3307 l
h
f*
385.285 498.3307 m
390.0472 498.3307 l
h
f*
274.1102 472.3087 m
278.8724 472.3087 l
h
f*
283.2945 472.3087 m
288.0567 472.3087 l
h
f*
277.7386 446.3433 m
282.5008 446.3433 l
h
f*
264.1323 420.3213 m
268.8945 420.3213 l
h
f*
273.3165 420.3213 m
282.8409 420.3213 l
h
f*
301.663 394.2992 m
306.4252 394.2992 l
h
f*
534.3874 381.3165 m
539.1496 381.3165 l
h
f*
271.3323 355.3512 m
280.8567 355.3512 l
h
f*
259.2 203.1307 m
278.7591 203.1307 l
h
f*
285.222 190.148 m
294.7465 190.148 l
h
f*
299.1685 190.148 m
308.6929 190.148 l
h
f*
243.9496 164.126 m
248.6551 164.126 l
h
f*
253.1339 164.126 m
262.6583 164.126 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(VP1,)Tj
2.1713 0 Td
(VP2,)Tj
2.177 0 Td
(VP3)Tj
1.9502 0 Td
(and)Tj
1.7291 0 Td
(VP4,)Tj
2.177 0 Td
(and)Tj
1.7291 0 Td
(eleven)Tj
2.7383 0 Td
(different)Tj
3.6567 0 Td
(mature)Tj
3.0954 0 Td
(non-structural)Tj
6.0321 0 Td
(proteins,)Tj
3.7417 0 Td
(NSP-3A)Tj
3.4979 0 Td
(among)Tj
-34.6958 -1.3039 Td
(them)Tj
2.2903 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
1.5988 0 Td
(FMDV)Tj
3.0727 0 Td
(has)Tj
1.542 0 Td
(seven)Tj
2.4321 0 Td
(immunologically)Tj
6.9959 0 Td
(distinct)Tj
3.2145 0 Td
(serotypes,)Tj
4.1612 0 Td
(namely)Tj
3.1464 0 Td
(O,)Tj
1.1963 0 Td
(A,)Tj
1.1281 0 Td
(C,)Tj
1.1055 0 Td
(SAT1,)Tj
2.6929 0 Td
(SAT2,)Tj
-34.5767 -1.2982 Td
(SAT3)Tj
2.4661 0 Td
(and)Tj
1.7291 0 Td
(Asia)Tj
1.9672 0 Td
(1.)Tj
0.9185 0 Td
(This)Tj
1.9899 0 Td
(virus)Tj
2.1996 0 Td
(produces)Tj
3.8778 0 Td
(a)Tj
0.6576 0 Td
(highly)Tj
2.7099 0 Td
(transmissible)Tj
5.4822 0 Td
(and)Tj
1.7291 0 Td
(devastating)Tj
4.7339 0 Td
(disease)Tj
3.016 0 Td
(of)Tj
1.0148 0 Td
(farm)Tj
-34.4917 -1.2983 Td
(animals,)Tj
3.5546 0 Td
(foot-and-mouth)Tj
6.7124 0 Td
(Disease)Tj
3.2258 0 Td
(\(FMD\),)Tj
3.2825 0 Td
(which)Tj
2.6475 0 Td
(is)Tj
0.8504 0 Td
(the)Tj
1.4683 0 Td
(most)Tj
2.2054 0 Td
(feared)Tj
2.6872 0 Td
(animal)Tj
2.9707 0 Td
(disease)Tj
3.016 0 Td
(worldwide,)Tj
-32.6208 -1.2983 Td
(causing)Tj
3.2484 0 Td
(large)Tj
2.16 0 Td
(economic)Tj
4.1386 0 Td
(losses)Tj
2.4774 0 Td
(during)Tj
2.931 0 Td
(an)Tj
1.2019 0 Td
(outbreak.)Tj
-14.9611 -1.3039 Td
(There)Tj
2.5795 0 Td
(is)Tj
0.8504 0 Td
(great)Tj
2.211 0 Td
(disparity)Tj
3.719 0 Td
(in)Tj
1.0318 0 Td
(progress)Tj
3.6 0 Td
(towards)Tj
3.4015 0 Td
(FMD)Tj
2.3811 0 Td
(control)Tj
3.1181 0 Td
(and)Tj
1.7291 0 Td
(eradication.)Tj
4.9493 0 Td
(While)Tj
2.6532 0 Td
(some)Tj
-33.4202 -1.2982 Td
(countries)Tj
3.9458 0 Td
(are)Tj
1.4513 0 Td
(either)Tj
2.5285 0 Td
(FMD)Tj
2.3754 0 Td
(free)Tj
1.7291 0 Td
(or)Tj
1.0998 0 Td
(well)Tj
1.8199 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(road)Tj
2.0579 0 Td
(to)Tj
1.0262 0 Td
(achieving)Tj
4.0308 0 Td
(eradication,)Tj
4.9493 0 Td
(others)Tj
2.7099 0 Td
(are)Tj
1.4456 0 Td
(at)Tj
0.9525 0 Td
(an)Tj
-34.8659 -1.2983 Td
(early)Tj
2.1486 0 Td
(stage)Tj
2.1997 0 Td
(of)Tj
1.0148 0 Td
(FMD)Tj
2.3811 0 Td
(control.)Tj
3.3448 0 Td
(In)Tj
1.1112 0 Td
(endemic)Tj
3.651 0 Td
(areas,)Tj
2.4718 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(Asia)Tj
1.9673 0 Td
(Africa)Tj
2.6872 0 Td
(and)Tj
1.7291 0 Td
(South)Tj
2.5568 0 Td
(America,)Tj
3.8665 0 Td
(FMD)Tj
-34.2026 -1.3039 Td
(control)Tj
3.118 0 Td
(is)Tj
0.8504 0 Td
(performed)Tj
4.4674 0 Td
(by)Tj
1.1849 0 Td
(regular)Tj
3.0557 0 Td
(vaccination)Tj
4.8302 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(inactivated)Tj
4.5978 0 Td
(whole-virus.)Tj
5.1646 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
1.5988 0 Td
(The)Tj
1.7858 0 Td
(limita-)Tj
-34.401 -1.2983 Td
(tions)Tj
2.1996 0 Td
(shown)Tj
2.8517 0 Td
(by)Tj
1.1792 0 Td
(these)Tj
2.2563 0 Td
(conventional)Tj
5.4255 0 Td
(vaccines)Tj
3.5546 0 Td
(have)Tj
2.058 0 Td
(prompted)Tj
4.2066 0 Td
(the)Tj
1.4683 0 Td
(study)Tj
2.3867 0 Td
(of)Tj
1.0148 0 Td
(new,)Tj
2.1033 0 Td
(safer)Tj
2.0977 0 Td
(alternative)Tj
-32.8023 -1.2983 Td
(vaccines)Tj
3.5546 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(].)Tj
1.5987 0 Td
(Synthetic)Tj
3.9401 0 Td
(peptides)Tj
3.5547 0 Td
(are)Tj
1.4513 0 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(most)Tj
2.2053 0 Td
(promising)Tj
4.3427 0 Td
(vaccine)Tj
3.1974 0 Td
(candidates)Tj
4.4618 0 Td
(for)Tj
1.3889 0 Td
(infec-)Tj
-33.8794 -1.3039 Td
(tious)Tj
2.1769 0 Td
(disease,)Tj
3.2485 0 Td
(such)Tj
2.058 0 Td
(as)Tj
1.0148 0 Td
(FMD,)Tj
2.6022 0 Td
(as)Tj
1.0147 0 Td
(they)Tj
1.9219 0 Td
(are)Tj
1.4514 0 Td
(highly)Tj
2.7099 0 Td
(pure,)Tj
2.2847 0 Td
(defined,)Tj
3.4525 0 Td
(stable)Tj
2.4889 0 Td
(and)Tj
1.7291 0 Td
(safe.)Tj
1.9502 0 Td
(Moreover,)Tj
4.3993 0 Td
(recent)Tj
-34.503 -1.2982 Td
(studies)Tj
2.9876 0 Td
(have)Tj
2.058 0 Td
(shown)Tj
2.846 0 Td
(that)Tj
1.7801 0 Td
(synthetic)Tj
3.8211 0 Td
(peptides)Tj
3.5603 0 Td
(achieve)Tj
3.1691 0 Td
(protective)Tj
4.2066 0 Td
(immunity)Tj
4.2236 0 Td
(against)Tj
3.0274 0 Td
(challenge)Tj
3.9571 0 Td
(in)Tj
-35.6369 -1.2983 Td
(swine)Tj
2.5058 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2585 0 Td
(4)Tj
0 g
(].)Tj
1.2586 0 Td
(On)Tj
1.5194 0 Td
(the)Tj
1.4683 0 Td
(other)Tj
2.3471 0 Td
(hand,)Tj
2.4831 0 Td
(differentiation)Tj
5.9811 0 Td
(between)Tj
3.5263 0 Td
(vaccinated)Tj
4.456 0 Td
(from)Tj
2.2053 0 Td
(infected)Tj
3.4186 0 Td
(animals)Tj
3.3335 0 Td
(is)Tj
-35.7616 -1.3039 Td
(feasible)Tj
3.1691 0 Td
(with)Tj
1.9955 0 Td
(such)Tj
2.0637 0 Td
(vaccines.)Tj
-6.0321 -1.2983 Td
(Linear)Tj
2.8062 0 Td
(peptides)Tj
3.5547 0 Td
(containing)Tj
4.5297 0 Td
(an)Tj
1.2019 0 Td
(immunodominant)Tj
7.6591 0 Td
(B-cell)Tj
2.4889 0 Td
(site)Tj
1.5703 0 Td
(located)Tj
3.0784 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(GH)Tj
1.7064 0 Td
(loop)Tj
1.9956 0 Td
(around)Tj
-34.2933 -1.2982 Td
(at)Tj
0.9524 0 Td
(positions)Tj
3.8551 0 Td
(140160)Tj
3.5886 0 Td
(of)Tj
1.0148 0 Td
(capsid)Tj
2.7496 0 Td
(protein)Tj
3.1521 0 Td
(VP1)Tj
1.9502 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2643 0 Td
(6)Tj
0 g
(])Tj
1.0318 0 Td
(can)Tj
1.6271 0 Td
(protect)Tj
3.0614 0 Td
(against)Tj
3.0273 0 Td
(FMDV)Tj
3.0728 0 Td
(challenge.)Tj
4.1839 0 Td
(How-)Tj
-34.5314 -1.2983 Td
(ever,)Tj
2.1146 0 Td
(the)Tj
1.474 0 Td
(protection)Tj
4.3823 0 Td
(conferred)Tj
4.1046 0 Td
(by)Tj
1.1792 0 Td
(these)Tj
2.2563 0 Td
(peptides)Tj
3.5547 0 Td
(is)Tj
0.8447 0 Td
(limited)Tj
3.0727 0 Td
(due,)Tj
1.9219 0 Td
(among)Tj
2.9934 0 Td
(other)Tj
2.3527 0 Td
(factors,)Tj
3.1238 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(lack)Tj
-35.8693 -1.3039 Td
(of)Tj
1.0147 0 Td
(T-cell)Tj
2.5172 0 Td
(epitopes)Tj
3.5376 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(7)Tj
0 g
(].)Tj
1.2642 0 Td
(Therefore,)Tj
4.3937 0 Td
(an)Tj
1.2019 0 Td
(effective)Tj
3.5093 0 Td
(peptide)Tj
3.1917 0 Td
(vaccine)Tj
3.1975 0 Td
(needs)Tj
2.5058 0 Td
(multivalency)Tj
5.3631 0 Td
(of)Tj
1.0148 0 Td
(B-cell)Tj
-33.9701 -1.2983 Td
(epitopes)Tj
3.5319 0 Td
(to)Tj
1.0261 0 Td
(elicit)Tj
2.1487 0 Td
(a)Tj
0.6519 0 Td
(high)Tj
2.007 0 Td
(neutralizing)Tj
5.0343 0 Td
(antibody)Tj
3.7587 0 Td
(response)Tj
3.736 0 Td
(and)Tj
1.7291 0 Td
(T-cell)Tj
2.5229 0 Td
(epitopes)Tj
3.5319 0 Td
(that)Tj
1.7801 0 Td
(provide)Tj
3.2882 0 Td
(ade-)Tj
-34.7468 -1.2983 Td
(quate)Tj
2.4094 0 Td
(cooperation)Tj
5.0229 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(].)Tj
1.6044 0 Td
(Multiple)Tj
3.6397 0 Td
(antigenic)Tj
3.8948 0 Td
(peptides)Tj
3.5546 0 Td
(\(MAPs\),)Tj
3.6227 0 Td
(also)Tj
1.7688 0 Td
(named)Tj
2.9707 0 Td
(dendrimers,)Tj
5.0853 0 Td
(are)Tj
1.4513 0 Td
(radial)Tj
-35.0246 -1.3039 Td
(or)Tj
1.0941 0 Td
(wedge-like)Tj
4.5298 0 Td
(branched)Tj
3.9854 0 Td
(macromolecules)Tj
6.7521 0 Td
(that)Tj
1.7802 0 Td
(contain)Tj
3.2428 0 Td
(a)Tj
0.6576 0 Td
(peptide)Tj
3.1918 0 Td
(core)Tj
1.9446 0 Td
(attached)Tj
3.5886 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
0.652 0 Td
(define)Tj
2.6986 0 Td
(num-)Tj
-35.1437 -1.2982 Td
(ber)Tj
1.5193 0 Td
(of)Tj
1.0148 0 Td
(epitopes)Tj
3.5376 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(10)Tj
0 g
(].)Tj
1.7348 0 Td
(Pigs)Tj
1.8765 0 Td
(vaccinated)Tj
4.456 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.652 0 Td
(dendrimeric)Tj
5.193 0 Td
(peptide,)Tj
3.4186 0 Td
(which)Tj
2.6532 0 Td
(included)Tj
3.7077 0 Td
(the)Tj
1.474 0 Td
(T-cell)Tj
-34.4917 -1.2983 Td
(epitope)Tj
3.1634 0 Td
(2135)Tj
2.6362 0 Td
(from)Tj
2.1997 0 Td
(3A)Tj
1.3719 0 Td
(and)Tj
1.7235 0 Td
(four)Tj
1.9105 0 Td
(copies)Tj
2.7099 0 Td
(of)Tj
1.0092 0 Td
(the)Tj
1.4626 0 Td
(B-cell)Tj
2.4832 0 Td
(site)Tj
1.5647 0 Td
(VP1)Tj
1.9445 0 Td
([136154],)Tj
4.4901 0 Td
(were)Tj
2.1146 0 Td
(protected)Tj
4.0025 0 Td
(against)Tj
-34.7865 -1.3039 Td
(type)Tj
1.9105 0 Td
(C)Tj
0.8844 0 Td
(FMDV)Tj
3.0727 0 Td
(challenge)Tj
3.9572 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
1.6044 0 Td
(Recent)Tj
2.9593 0 Td
(studies)Tj
2.982 0 Td
(indicated)Tj
3.9402 0 Td
(that)Tj
1.7801 0 Td
(a)Tj
0.652 0 Td
(similar)Tj
2.9877 0 Td
(construct)Tj
3.9798 0 Td
(incorporating)Tj
-30.7103 -1.2983 Td
(the)Tj
1.4683 0 Td
(B)Tj
0.7994 0 Td
(cell)Tj
1.559 0 Td
(site)Tj
1.5704 0 Td
(sequence)Tj
3.8607 0 Td
(from)Tj
2.2054 0 Td
(type)Tj
1.9105 0 Td
(O)Tj
0.9695 0 Td
(FMDV)Tj
3.0727 0 Td
(O-UKG)Tj
3.4412 0 Td
(induced)Tj
3.464 0 Td
(full)Tj
1.5307 0 Td
(protection)Tj
4.3823 0 Td
(in)Tj
1.0318 0 Td
(pigs)Tj
1.8312 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(].)Tj
-31.9009 -1.2983 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(report,)Tj
2.9366 0 Td
(novel)Tj
2.3981 0 Td
(dendrimeric)Tj
5.1931 0 Td
(peptides)Tj
3.5546 0 Td
(were)Tj
2.1203 0 Td
(designed)Tj
3.7644 0 Td
(containing)Tj
4.5297 0 Td
(a)Tj
0.652 0 Td
(bovine)Tj
2.931 0 Td
(T-cell)Tj
2.5228 0 Td
(epitope)Tj
-34.5824 -1.2982 Td
(2140)Tj
2.6362 0 Td
(from)Tj
2.211 0 Td
(VP1)Tj
1.9445 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
1.8539 0 Td
(linked)Tj
2.7269 0 Td
(to)Tj
1.0261 0 Td
(two)Tj
1.7121 0 Td
(\(B)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 350.3055 354.7275 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 353.8771 356.4283 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(T\))Tj
1.1678 0 Td
(or)Tj
1.0999 0 Td
(four)Tj
1.9162 0 Td
(\(B)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 404.9007 354.7275 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 408.4724 356.4283 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(T\))Tj
1.1678 0 Td
(copies)Tj
2.7213 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(B-cell)Tj
2.4888 0 Td
(site)Tj
1.5704 0 Td
(VP1)Tj
1.9502 0 Td
([135160])Tj
-33.2274 -1.3039 Td
(from)Tj
2.2053 0 Td
(FMDV)Tj
3.0728 0 Td
(O1)Tj
1.44 0 Td
(Campos)Tj
3.5206 0 Td
(assembled)Tj
4.3256 0 Td
(using)Tj
2.3868 0 Td
(a)Tj
0.6576 0 Td
(maleimide)Tj
4.4446 0 Td
(conjugation.)Tj
5.2327 0 Td
(A)Tj
0.9014 0 Td
(pilot)Tj
2.058 0 Td
(study)Tj
2.3867 0 Td
(was)Tj
1.7008 0 Td
(per-)Tj
-34.3329 -1.2982 Td
(formed)Tj
3.1578 0 Td
(to)Tj
1.0261 0 Td
(address)Tj
3.2258 0 Td
(the)Tj
1.4684 0 Td
(immunogenicity)Tj
6.8541 0 Td
(of)Tj
1.0148 0 Td
(such)Tj
2.0636 0 Td
(dendrimeric)Tj
5.1873 0 Td
(vaccines)Tj
3.5602 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(protection)Tj
-30.7556 -1.2983 Td
(afforded)Tj
3.583 0 Td
(in)Tj
1.0374 0 Td
(cattle)Tj
2.3471 0 Td
(against)Tj
3.0274 0 Td
(viral)Tj
1.9899 0 Td
(challenge.)Tj
-10.7886 -1.3039 Td
(Our)Tj
1.8709 0 Td
(results)Tj
2.8062 0 Td
(show)Tj
2.3018 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.4683 0 Td
(first)Tj
1.8085 0 Td
(time)Tj
2.0296 0 Td
(that)Tj
1.7745 0 Td
(not)Tj
1.576 0 Td
(only)Tj
1.9786 0 Td
(tetravalent)Tj
4.4503 0 Td
(presentation)Tj
5.2157 0 Td
(of)Tj
1.0148 0 Td
(B-cell)Tj
2.4888 0 Td
(epitopes)Tj
-33.3635 -1.2983 Td
(linked)Tj
2.7269 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(T-bovine)Tj
3.8891 0 Td
(epitope)Tj
3.1748 0 Td
(but)Tj
1.5534 0 Td
(also)Tj
1.7688 0 Td
(bivalent)Tj
3.4015 0 Td
(formulation)Tj
5.0342 0 Td
(results)Tj
2.8063 0 Td
(in)Tj
1.0375 0 Td
(an)Tj
1.2018 0 Td
(effective)Tj
3.5093 0 Td
(vaccine)Tj
3.1975 0 Td
(that)Tj
-35.7956 -1.2982 Td
(conferred)Tj
4.1045 0 Td
(protection)Tj
4.3824 0 Td
(in)Tj
1.0318 0 Td
(cattle.)Tj
2.5738 0 Td
(Thus,)Tj
2.4718 0 Td
(these)Tj
2.2507 0 Td
(synthetic)Tj
3.8268 0 Td
(peptides)Tj
3.5545 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
1.1508 0 Td
(considered)Tj
4.5978 0 Td
(promising)Tj
4.3426 0 Td
(vac-)Tj
-35.9146 -1.304 Td
(cine)Tj
1.8822 0 Td
(candidates)Tj
4.4674 0 Td
(with)Tj
1.9955 0 Td
(reasonable)Tj
4.4731 0 Td
(prospects)Tj
4.0025 0 Td
(of)Tj
1.0148 0 Td
(clinical)Tj
3.0726 0 Td
(application.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 239.1874 cm
BT
/F2 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 -1.4976 Td
(Dendrimeric)Tj
5.5417 0 Td
(peptides)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 204.2078 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Two)Tj
2.0182 0 Td
(peptides)Tj
3.5603 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8198 0 Td
(1)Tj
0 g
(\))Tj
1.0318 0 Td
(incorporating)Tj
5.7487 0 Td
(a)Tj
0.6519 0 Td
(T-cell)Tj
2.5228 0 Td
(epitope)Tj
3.1748 0 Td
([VP1)Tj
2.2904 0 Td
(\(2140\)])Tj
3.6567 0 Td
(immunodominant)Tj
7.6648 0 Td
(for)Tj
-34.1402 -1.2982 Td
(bovine)Tj
2.9253 0 Td
(lymphocytes)Tj
5.2554 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(12)Tj
0 g
(])Tj
1.5137 0 Td
(and)Tj
1.7291 0 Td
(two)Tj
1.7121 0 Td
(or)Tj
1.0942 0 Td
(four)Tj
1.9162 0 Td
(copies)Tj
2.7156 0 Td
(of)Tj
1.0204 0 Td
(the)Tj
1.4684 0 Td
(B-cell)Tj
2.4888 0 Td
(epitope)Tj
3.1747 0 Td
([site)Tj
1.9106 0 Td
(AVP1)Tj
3.1464 0 Td
(\(135)Tj
-33.8057 -1.3039 Td
(160\)],)Tj
2.5511 0 Td
(termed)Tj
3.0841 0 Td
(B)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 262.148 176.5417 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 265.7196 178.1858 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(T)Tj
0.8333 0 Td
(or)Tj
1.0942 0 Td
(B)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 290.8346 176.5417 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 294.3496 178.1858 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(T,)Tj
1.0601 0 Td
(respectively,)Tj
5.108 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(dendrimeric)Tj
5.1931 0 Td
(arrangement)Tj
5.3574 0 Td
(were)Tj
2.1203 0 Td
(synthesized)Tj
4.8302 0 Td
(as)Tj
-34.7921 -1.2982 Td
(described)Tj
4.0535 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(13)Tj
0 g
(].)Tj
1.7348 0 Td
(The)Tj
1.7858 0 Td
(C-terminal)Tj
4.643 0 Td
(Cys)Tj
1.6951 0 Td
(side)Tj
1.8029 0 Td
(chain)Tj
2.4207 0 Td
(thiol)Tj
2.0636 0 Td
(is)Tj
0.8504 0 Td
(linked)Tj
2.7269 0 Td
(to)Tj
1.0262 0 Td
(Lys)Tj
1.576 0 Td
(via)Tj
1.372 0 Td
(a)Tj
0.6576 0 Td
(3-maleimidopro-)Tj
-29.6671 -1.2983 Td
(pionic)Tj
2.7496 0 Td
(acid)Tj
1.8709 0 Td
(unit;)Tj
2.0862 0 Td
(the)Tj
1.474 0 Td
(peptides)Tj
3.5546 0 Td
(were)Tj
2.1203 0 Td
(purified)Tj
3.4129 0 Td
(by)Tj
1.1792 0 Td
(HPLC)Tj
2.7496 0 Td
(and)Tj
1.7291 0 Td
(characterized)Tj
5.5558 0 Td
(by)Tj
1.1849 0 Td
(mass)Tj
2.194 0 Td
(spectrometry.)Tj
-31.8611 -1.3039 Td
(Sequences)Tj
4.3313 0 Td
(are)Tj
1.4513 0 Td
(derived)Tj
3.2145 0 Td
(from)Tj
2.2053 0 Td
(FMDV)Tj
3.0727 0 Td
(O1)Tj
1.44 0 Td
(Campos.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 112.9889 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Virus)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(FMDV)Tj
3.0727 0 Td
(O1)Tj
1.44 0 Td
(Campos)Tj
3.5206 0 Td
(was)Tj
1.7008 0 Td
(kindly)Tj
2.7609 0 Td
(provided)Tj
3.8154 0 Td
(by)Tj
1.1792 0 Td
(Biogenesis)Tj
4.4277 0 Td
(Bago)Tj
0 Tc
1.542 0.0566 Td
()Tj
-0.004 Tc
0.6633 -0.0566 Td
(S.A.)Tj
1.8312 0 Td
(as)Tj
1.0148 0 Td
(binary)Tj
2.8006 0 Td
(ethylene-imine)Tj
-29.7692 -1.2982 Td
(\(BEI\)-inactivated)Tj
7.1149 0 Td
(\(iFMDV\).)Tj
4.2462 0 Td
(Purified)Tj
3.4526 0 Td
(virus)Tj
2.1997 0 Td
(was)Tj
1.7008 0 Td
(obtained)Tj
3.7303 0 Td
(by)Tj
1.1792 0 Td
(a)Tj
0.6577 0 Td
(sucrose)Tj
3.1918 0 Td
(density)Tj
3.101 0 Td
(gradient)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 427.4078 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Protection)Tj
4.6488 0 Td
(of)Tj
1.0417 0 Td
(cattle)Tj
2.5654 0 Td
(by)Tj
1.2614 0 Td
(dendrim)Tj
3.5434 0 Td
(eric)Tj
1.8 0 Td
(peptides)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01851)Tj
4.089 0 Td
(84)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(26,)Tj
1.5874 0 Td
(2017)Tj
32.2798 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(16)Tj
/F9 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.7929 0 Td
(collection)Tj
3.7418 0 Td
(and)Tj
1.5874 0 Td
(analysis,)Tj
3.4087 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
-16.7245 -1.3748 Td
(publish,)Tj
3.1464 0 Td
(or)Tj
0.9993 0 Td
(preparation)Tj
4.4433 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F8 1 Tf
-10.9063 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F9 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3749 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
BT
10.3394 79.2147 Td
(exist.)Tj
ET
Q
endstream
endobj
54 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 56 0 R/Contents 57 0 R/TrimBox[0 0 612 792]>>
endobj
55 0 obj
<>stream
x{T?pDEQT*S*%DSJ:\3:RJtI%
JId4dR$&FH߯{ff}]||}_^^{^@A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A @A O?T@A @A @L;V[#?[OA @A @A |T>(<@A @A @A F>2#* @A @A &Ck Q* @A @A aGîO @A @A @uv.xE|ʮxZA @A @A j~}Pٔ~;zի^W}/9Wկ{: @A @A @{!H旾gyYgWwA̶۫wݚxғG=Nu}{=A裐OA @A @A >e3o%A}wk^%{>ysw9?}>SQT0M B9təߎf. HC@A @GbE}sϼ|gs9o~?y▿}|,髷s4y}_/BA/a9J '
9((2ퟺ~ݾ?vZMtDk19;xC@A @AB $E(eA @A @A VLr+]A @A @A %h@A @A @}YE@A @A @KQt.9ҦחҦ[{*RW5/&Cvy+, s*QҁRT}];]ٽ:J/]o\%RYxe?IS_WqrqC@A qA3}K}E/.j./o'WZñк܅QBW}
U{²xeO7UOUS5Wu+TMק
0VWSYV$6a5^P@kvy}*kc֕'!OGlwRQӍ;5ީ.e]Y0=Ic*Vq7@.BA @A`^^>[?=;m)V
Mrƚ[QYmw o;8W/J2W-rۿoDWoo٢U.9;N-^?Rzo7?/VKir|#n ŊoI@A @vHלTS.
}uS$uUtw)x{~SUŦ:M^zqq,VJvy8r:$*փ>{ۿgk&(IN @A 3Oc_z|69:~p_Ϟg?O|ғOa&ZcP}
@]p2TwL}W١j"%S_ ]n\j[ٕ&[U}\t{ӛTڷ#j+. DC(GQr}Dkݰ;^T6/}{>I_ukpgU%آ~t99(G>`}=f&\=ymvYg;swDb벺ĖF4RA @AF@tce»w8!>[pس{ǟJΪ4w>
-{G^^N;?~Ozի~~%u[˿˿뻾wwa8,mWUuqx~+l,mF%sotzWW詳>WooX[k؞|^ww$MX!F IM#ضv5
=Z_mLiQ-M8F9w.}^ShxbTۤuc ?ʯ=y.I-Ot/bx|W~W~ڧ}?a{ӛ4j6S=b]W0g??ɣ:3X{_e_=N]RsR,!\Ve/{xԣeorw݈:`V+K/83ue5@;7B
A @ADC`K'.(z3.oƓdTϯگ i{>%{V
w)aQ=B?
WxEĔ̽@uIB{~~_=M%2~p\}<h?=2Brd2#T]U4ןeg݂]?3~g~d"4ǞUCwo5#T{cL|<xՌ{e ^"(J7KJ$ MI
?u2S{ǯI_<7ns5oi%}e$gy
KqȎZ~~ۿoy[7u n9RdV+eCUm"Qtwa:2UrsT븥H)3KI-v,=zdjh4E//b|WW?9q>]?u8bqK]
0nO_Dsp~woo1,vq@ԟʽKM_K-j{ʻT[l@?WU @A زIPcьw]E__!s싾мJ.nyګ^khO)&iڪr;J
O|:L NR?3?XK(P-/~nxJDkK}jUV?_9SYԍo|cM}d]JJֵ WU??}}r;;4կ~7|nt}7}]glԨ:f8D}W}ߑ
{M:QЦȷ7P|~|ʧГrhK7qLU~[R.ue_ Qme
0Q C{{oq[wk}$dBoۡo_ŶErIl/-d,kFdZn9UX㢆X./yS菚ū:Q]UخLUZW!/؏X*N:ݝRi0֬ݦj-g-]gY0|N
pz/Id)1:
sd/́f4Є&}?I;yK_ٟٵpekP-NxE`p[V4ԡ+]J,X+c2OM*L?-v駾EGMզJ.jnR_jc[:mSZV @A p| P[վȪA'wus
>>]rQBﶷCg=Yh7;cҪbM'I%A~0MiDj(auXp;V-e\Jy;.\;N8@g&j+:~,9է(Ho|{9B81v!c%j⺽`-__MnI|Iʢ=!3TࣀR) q!\7W4u3&(S$=aLU8sAa$cwjgDQUGpKCݖ>DpOU006#'g
ڕ?-ZYN^|)[[eG5R`)Js㍛3VvY~73+-}k;א<
uTw2T
R*ПU_'{~u?Ku%v3'yx1e6As.M%_7ii<*|wy*,^`uR<@8CSEj/2[,L=;C`Py>^٢ÖJ
Ֆ2ZMQ`k՚WaS-s͍~
GKIxRxrWkA @8S6HBlmH6N!$ 61Nˆ\m~-VF!6,"jw3N^{.Ƶo7K $j{1S66fPc5V@SZjMM_wTɩiԧ>٨c=2RN`{ZL7z.=uhCLyoNvv$xee%Rֺ]@??oZ;VX-]Dq
K^^Usk»|(@A @8Ծ}RMRatEB}Ez8+n6F罻T(l]n?jur,%&s
/M8r>诎&vS٥M<=俷Ӷ٤>AzOXҨx-yeM!+