Modeling Dengue Immune Responses Mediated by Antibodies: Insights on the Biological Parameters to Describe Dengue Infections

<div>Model simulation for secondary dengue infection with a homologous serotype: immunological responses mediated by antibodies. Overall viral particles are plotted in red: free virus and Antibody-DENV complexes (<svg height="12.0653pt" id="M98" style="vertical-align:-3.4294pt" version="1.1" viewbox="-0.0498162 -8.6359 90.6273 12.0653" width="90.6273pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.262,0)"><path d="M546 430L539 434C529 434 505 438 495 440C473 444 450 448 430 448C352 448 265 412 213 366C145 306 96 203 96 103C96 22 135 -12 160 -12C190 -12 238 14 262 32C310 68 368 120 411 184H413C403 117 396 75 384 21C353 -118 325 -158 291 -184C270 -200 241 -205 208 -205C133 -205 90 -164 74 -110C70 -98 58 -100 49 -107C34 -119 23 -140 23 -155C23 -190 74 -261 166 -261C219 -261 280 -233 314 -208C383 -157 446 -79 470 81C491 223 529 388 546 430ZM456 386C452 357 433 283 420 252C402 216 366 174 325 129C288 88 239 56 212 56C192 56 182 77 182 120C182 165 199 242 226 292C256 348 281 377 311 389C327 395 353 402 375 402C408 402 436 394 456 386Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.66,0)"><path d="M962 650H795L470 145L347 650H176L170 622C268 613 275 606 244 503L190 322C150 188 132 126 118 91C102 50 80 33 18 28L12 0H245L251 28C175 35 170 48 174 93C177 128 191 180 220 284L292 542H294C331 392 383 150 409 4H432L774 555H776L714 137C700 40 694 34 612 28L606 0H868L874 28C793 34 784 37 797 137L849 533C859 612 863 616 956 622L962 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,27.373,0)"><path d="M535 230V280H52V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.91,0)"><path d="M743 375C743 570 607 650 407 650H136L130 622C214 612 220 606 204 526L125 122C110 43 105 36 24 27L17 0H250C382 0 482 23 571 76C680 141 743 248 743 375ZM644 379C644 188 520 36 305 36C277 36 249 38 229 46C205 55 202 71 212 126L293 553C300 588 306 600 317 606C330 613 356 617 390 617C547 617 644 537 644 379Z"></path></g><g transform="matrix(.013,0,0,-0.013,47.476,0)"><path d="M593 650H142L136 622C219 616 224 611 209 531L130 120C114 39 108 34 23 28L17 0H501C518 32 557 130 568 158L540 169C519 132 495 93 469 70C439 43 409 35 332 35C272 35 241 37 225 50C211 61 211 89 222 149L253 320H350C441 320 443 312 441 239H471L510 434H481C455 366 448 358 360 358H260L303 572C311 613 312 615 348 615H431C509 615 522 603 532 581C544 555 546 531 545 491L574 493C583 555 592 631 593 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,55.093,0)"><path d="M822 650H589L583 622C660 617 677 607 674 561C672 534 664 481 647 390L600 137H596L273 650H126L120 622C176 620 194 615 207 594C221 571 225 557 214 504L161 257C141 166 129 112 121 85C108 42 83 30 29 28L23 0H260L266 28C193 33 173 42 176 89C178 122 186 172 202 255L256 527H259L583 -8H612L690 390C708 481 720 535 728 558C744 603 756 619 816 622L822 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,66.003,0)"><path d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,78.133,0)"><path d="M170 255C170 288 146 313 114 313S58 288 58 255C58 221 82 198 114 198S170 221 170 255Z"></path></g><g transform="matrix(.013,0,0,-0.013,84.002,0)"><path d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"></path></g></svg> + <svg height="12.0653pt" id="M99" style="vertical-align:-3.4294pt" version="1.1" viewbox="-0.0498162 -8.6359 71.9111 12.0653" width="71.9111pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M405 650H141L135 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472 243 631 441 631C557 631 617 583 617 469L647 472C650 545 655 604 658 632C625 643 554 666 467 666C201 666 23 502 23 278C23 90 156 -16 339 -16C410 -16 501 6 569 24C566 43 567 70 573 101L589 183C604 259 607 262 667 271L673 297Z"></path></g><g transform="matrix(.013,0,0,-0.013,23.719,0)"><path d="M535 230V280H52V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,34.256,0)"><path d="M743 375C743 570 607 650 407 650H136L130 622C214 612 220 606 204 526L125 122C110 43 105 36 24 27L17 0H250C382 0 482 23 571 76C680 141 743 248 743 375ZM644 379C644 188 520 36 305 36C277 36 249 38 229 46C205 55 202 71 212 126L293 553C300 588 306 600 317 606C330 613 356 617 390 617C547 617 644 537 644 379Z"></path></g><g transform="matrix(.013,0,0,-0.013,43.822,0)"><path d="M593 650H142L136 622C219 616 224 611 209 531L130 120C114 39 108 34 23 28L17 0H501C518 32 557 130 568 158L540 169C519 132 495 93 469 70C439 43 409 35 332 35C272 35 241 37 225 50C211 61 211 89 222 149L253 320H350C441 320 443 312 441 239H471L510 434H481C455 366 448 358 360 358H260L303 572C311 613 312 615 348 615H431C509 615 522 603 532 581C544 555 546 531 545 491L574 493C583 555 592 631 593 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.439,0)"><path d="M822 650H589L583 622C660 617 677 607 674 561C672 534 664 481 647 390L600 137H596L273 650H126L120 622C176 620 194 615 207 594C221 571 225 557 214 504L161 257C141 166 129 112 121 85C108 42 83 30 29 28L23 0H260L266 28C193 33 173 42 176 89C178 122 186 172 202 255L256 527H259L583 -8H612L690 390C708 481 720 535 728 558C744 603 756 619 816 622L822 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,62.349,0)"><path d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"></path></g></svg> + <span class="nowrap"><svg height="8.8423pt" id="M100" style="vertical-align:-0.2064009pt" version="1.1" viewbox="-0.0498162 -8.6359 9.35121 8.8423" width="9.35121pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"></path></g></svg>).</span> Free IgM is shown in magenta and free IgG in green. Antibody-DENV complexes <svg height="12.0653pt" id="M101" style="vertical-align:-3.4294pt" version="1.1" viewbox="-0.0498162 -8.6359 75.5778 12.0653" width="75.5778pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,4.262,0)"><path d="M546 430L539 434C529 434 505 438 495 440C473 444 450 448 430 448C352 448 265 412 213 366C145 306 96 203 96 103C96 22 135 -12 160 -12C190 -12 238 14 262 32C310 68 368 120 411 184H413C403 117 396 75 384 21C353 -118 325 -158 291 -184C270 -200 241 -205 208 -205C133 -205 90 -164 74 -110C70 -98 58 -100 49 -107C34 -119 23 -140 23 -155C23 -190 74 -261 166 -261C219 -261 280 -233 314 -208C383 -157 446 -79 470 81C491 223 529 388 546 430ZM456 386C452 357 433 283 420 252C402 216 366 174 325 129C288 88 239 56 212 56C192 56 182 77 182 120C182 165 199 242 226 292C256 348 281 377 311 389C327 395 353 402 375 402C408 402 436 394 456 386Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.66,0)"><path d="M962 650H795L470 145L347 650H176L170 622C268 613 275 606 244 503L190 322C150 188 132 126 118 91C102 50 80 33 18 28L12 0H245L251 28C175 35 170 48 174 93C177 128 191 180 220 284L292 542H294C331 392 383 150 409 4H432L774 555H776L714 137C700 40 694 34 612 28L606 0H868L874 28C793 34 784 37 797 137L849 533C859 612 863 616 956 622L962 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,27.373,0)"><path d="M535 230V280H52V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.91,0)"><path d="M743 375C743 570 607 650 407 650H136L130 622C214 612 220 606 204 526L125 122C110 43 105 36 24 27L17 0H250C382 0 482 23 571 76C680 141 743 248 743 375ZM644 379C644 188 520 36 305 36C277 36 249 38 229 46C205 55 202 71 212 126L293 553C300 588 306 600 317 606C330 613 356 617 390 617C547 617 644 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36 24 27L17 0H250C382 0 482 23 571 76C680 141 743 248 743 375ZM644 379C644 188 520 36 305 36C277 36 249 38 229 46C205 55 202 71 212 126L293 553C300 588 306 600 317 606C330 613 356 617 390 617C547 617 644 537 644 379Z"></path></g><g transform="matrix(.013,0,0,-0.013,43.822,0)"><path d="M593 650H142L136 622C219 616 224 611 209 531L130 120C114 39 108 34 23 28L17 0H501C518 32 557 130 568 158L540 169C519 132 495 93 469 70C439 43 409 35 332 35C272 35 241 37 225 50C211 61 211 89 222 149L253 320H350C441 320 443 312 441 239H471L510 434H481C455 366 448 358 360 358H260L303 572C311 613 312 615 348 615H431C509 615 522 603 532 581C544 555 546 531 545 491L574 493C583 555 592 631 593 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.439,0)"><path d="M822 650H589L583 622C660 617 677 607 674 561C672 534 664 481 647 390L600 137H596L273 650H126L120 622C176 620 194 615 207 594C221 571 225 557 214 504L161 257C141 166 129 112 121 85C108 42 83 30 29 28L23 0H260L266 28C193 33 173 42 176 89C178 122 186 172 202 255L256 527H259L583 -8H612L690 390C708 481 720 535 728 558C744 603 756 619 816 622L822 650Z"></path></g><g transform="matrix(.013,0,0,-0.013,62.349,0)"><path d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"></path></g></svg> are shown in blue and orange, respectively. Parameter values used for the model simulation are available at [<a href="/journals/cmm/2022/8283239/#B22">22</a>], if not otherwise stated here.</div>

Computational and Mathematical Methods

fig7

Figure 7

Figure 7: Modeling Dengue Immune Responses Mediated by Antibodies: Insights on the Biological Parameters to Describe Dengue Infections 