IMPERFECT VACCINES AND THE EVOLUTION OF PATHOGENS CAUSING ACUTE INFECTIONS IN VERTEBRATES
Vitaly V. Ganusov
Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
Department of Biology, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322
E-mail: [email protected]
Search for more papers by this authorRustom Antia
Department of Biology, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322
Search for more papers by this authorVitaly V. Ganusov
Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
Department of Biology, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322
E-mail: [email protected]
Search for more papers by this authorRustom Antia
Department of Biology, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322
Search for more papers by this authorAbstract
Abstract A study by Gandon et al. (2001) considered the potential ways pathogens may evolve in response to vaccination with imperfect vaccines. In this paper, by focusing an acute infections of vertebrate hosts, we examine whether imperfect vaccines that do not completely block a pathogen's replication (antigrowth) or transmission (antitransmission) may lead to evolution of more or less virulent pathogen strains. To address this question, we use models of the within-host dynamics of the pathogen and the host's immune responses. One advantage of the use of this within-host approach is that vaccination can be easily incorporated in the models and the trade-offs between pathogen transmissibility, host recovery, and virulence that drive evolution of pathogens in these models can be easily estimated. We find that the use of either antigrowth or antitransmission vaccines leads to the evolution of pathogens with an increased within-host growth rate; infection of unvaccinated hosts with such evolved pathogens results in high host mortality and low pathogen transmission. Vaccination of only a fraction of hosts with antigrowth vaccines may prevent pathogens from evolving high virulence due to pathogen adaptation to unvaccinated hosts and thus protection of vaccinated hosts from pathogen-induced disease. In contrast, antitransmission vaccines may be beneficial only if they are effective enough to cause pathogen extinction. Our results suggest that particular mechanisms of action of vaccines and their efficacy are crucial in predicting longterm evolutionary consequences of the use of imperfect vaccines.
Literature Cited
- Anderson, R. M., and R. M. May. 1982. Coevolution of hosts and parasites. Parasitology 85: 411–426.
-
Anderson, R. M., and
R. M. May. 1991. Infectious diseases in humans: dynamics and control. Oxford Univ. Press,
Oxford
,
U.K.
10.1093/oso/9780198545996.001.0001 Google Scholar
- André, J. B., and S. Gandon. 2006. Vaccination, within-host dynamics and virulence evolution. Evolution 60: 13–23.
- André, J., J. Ferdy, and B. Godelle. 2003. Within-host parasite dynamics, emerging trade-off, and evolution of virulence with immune system. Evolution 57: 1489–1497.
- Antia, R., B. R. Levin, and R. M. May. 1994. Within-host population dynamics and the evolution and maintenance of microparsite virulence. Am. Nat. 144: 457–472.
- Blattman, J. N., R. Antia, D. J. Sourdive, X. Wang, S. M. Kaech, K. Murali-Krishna, J. D. Altman, and R. Ahmed. 2002. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J. Exp. Med. 195: 657–664.
- Bonhoeffer, S., and M. Nowak. 1994. Mutation and the evolution of virulence. Proc. R. Soc. Lond. B 258: 133–140.
- Bremermann, H. J., and H. R. Thieme. 1989. A competetive exclusion principle for pathogen virulence. J. Math. Biol. 27: 179–190.
- Brown, S., M. Hochberg, and B. Grenfell. 2002. Does multiple infection select for raised virulence Trends Microbiol. 10: 401–405.
- Christensen, J., P. Doherty, K. Branum, and J. Riberdy. 2000. Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory. J. Virol. 74: 11690–11696.
- Coban, C., M. Philipp, J. Purcell, D. Keister, M. Okulate, D. Martin, and N. Kumar. 2004. Induction of Plasmodium falciparum transmission-blocking antibodies in nonhuman primates by a combination of DNA and protein immunizations. Infect. Immunol. 72: 253–259.
- Day, T. 2002. On the evolution of virulence and the relationship between various measures of mortality. Proc. R. Soc. Lond. B 269: 1317–1323.
- Day, T. 2003. Virulence evolution and the timing of disease life-history events. Trends Ecol. Evol. 18: 113–118.
- Doherty, P. C., and J. P. Christensen. 2000. Accessing complexity: the dynamics of virus-specific T cell responses. Annu. Rev. Immunol. 18: 561–592.
- Druilhe, P., F. Spertini, D. Soesoe, G. Corradin, P. Mejia, S. Singh, R. Audran, A. Bouzidi, C. Oeuvray, and C. Roussilhon. 2005. A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum. PLoS Med. 2: e344.
- Dunachie, S., and A. Hill. 2003. Prime-boost strategies for malaria vaccine development. J. Exp. Biol. 206: 3771–3779.
- Ebert, D., and J. Bull. 2003. Challenging the trade-off model for the evolution of virulence: Is virulence management feasible Trends Microbiol. 11: 15–20.
- Fenner, F., M. Day, and G. Woodroofe. 1956. The epidemiological consequences of the mechanical transmission of myxomatosis by mosquitoes. J. Hyg. (Lond.) 54: 284–303.
- Flynn, K. J., J. M. Riberdy, J. P. Christensen, J. D. Altman, and P. C. Doherty. 1999. In vivo proliferation of naive and memory influenza-specific CD8(+) T cells. Proc. Natl. Acad. Sci. USA 96: 8597–8602.
- Frank, S. A. 1996. Models of parasite virulence. Q. Rev. Biol. 71: 37–78.
- Gandon, S., M. J. Mackinnon, S. Nee, and A. F. Read. 2001. Imperfect vaccines and the evolution of pathogen virulence. Nature 414: 751–756.
- Gandon, S., M. J. Mackinnon, S. Nee, and A. F. Read. 2002. Antitoxin vaccines and pathogen virulence: a reply. Nature 417: 610.
- Gandon, S., M. J. Mackinnon, S. Nee, and A. F. Read. 2003. Imperfect vaccination: some epidemiological and evolutionary consequences. Proc. R. Soc. Lond. B 270: 1129–1136.
- Ganusov, V., and R. Antia. 2003. Trade-offs and the evolution of virulence of microparasites: Do details matter Theor. Popul. Biol. 64: 211–220.
- Ganusov, V. V., C. T. Bergstrom, and R. Antia. 2002. Within-host population dynamics and the evolution of microparasites in a heterogeneous host population. Evolution 52: 213–223.
- Gilchrist, M., and A. Sasaki. 2002. Modeling host-parasite coevolution: a nested approach based on mechanistic models. J. Theor. Biol. 218: 289–308.
- Grayson, J. M., L. E. Harrington, J. G. Lanier, E. J. Wherry, and R. Ahmed. 2002. Differential sensitivity of naive and memory CD8(+) T cells to apoptosis in vivo. J. Immunol. 169: 3760–3770.
- Homann, D., L. Teyton, and M. Oldstone. 2001. Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory. Nat. Med. 7: 913–919.
- Levin, S., and D. Pimentel. 1981. Selection of intermediate rates of increase in parasite-host systems. Am. Nat. 117: 308–315.
- Mackinnon, M. J., and A. F. Read. 1999. Genetic relationship between parasite virulence and transmission in the rodent malaria Plasmodium chabaudi. Evolution 53: 689–703.
- Mackinnon, M. J., and A. F. Read. 2003. The effects of host immunity on virulence-transmissibility relationships in the rodent malaria parasite Plasmodium chabaudi. Parasitology 126: 103–112.
- May, R. M., and M. A. Nowak. 1995. Coinfection and the evolution of parasite virulence. Proc. R. Soc. Lond. B 261: 209–215.
- Mead-Briggs, A. R., and J. A. Vaughan. 1975. The differential transmissibility of Myxoma virus strains of differing virulence grades by the rabbit flea Spilopsyllus cuniculi (Dale). J. Hyg. (Lond.) 75: 237–247.
- Moingeon, P., J. Almond, and M. de Wilde. 2003. Therapeutic vaccines against infectious diseases. Curr. Opin. Microbiol. 6: 462–471.
- Murali-Krishna, K., J. Altman, M. Suresh, D. Sourdive, A. Zajac, J. Miller, J. Slansky, and R. Ahmed. 1998. Counting antigen-specific CD8+ T cells: a re-evaluation of bystander actiation during viral infection. Immunity 8: 177–187.
- Nowak, M. A., and R. M. May. 1994. Superinfection and the evolution of parasite virulence. Proc. R. Soc. Lond. B 255: 81–89.
- Sasaki, A., and Y. Iwasa. 1991. Optimal growth schedule of pathogens within a host: switching between lytic and latent cycles. Theor. Popul. Biol. 39: 201–239.
-
Schall, J. J.
2002. Parasite virulence. Pp. 283–313
in
E. E. Lewis,
J. F. Campbell, and
M. V. K. Sukhdeo, eds.
The behavioural ecology of parasites. CAB International,
New York
.
10.1079/9780851996158.0283 Google Scholar
- Schneerson, R., J. Robbins, J. Taranger, T. Lagergard, and B. Trollfors. 1996. A toxoid vaccine for pertussis as well as diphtheria? Lessons to be relearned. Lancet 348: 1289–1292.
- Schulman, J. L. 1967. Experimental transmission of influenza virus infection in mice. IV. Relationship of transmissibility of different strains of virus and recovery of airborne virus in the environment of infector mice. J. Exp. Med. 125: 479–488.
- Schulman, J. L. 1970. Effects of immunity on transmission of influenza: experimental studies. Prog. Med. Virol. 12: 128–160.
- Smith, T. 2002. Imperfect vaccines and imperfect models. Trends. Ecol. Evol. 14: 154–156.
- Soubeyrand, B., and S. Plotkin. 2002. Microbial evolution: antitoxin vaccines and pathogen virulence. Nature 417: 609–610.
- Taranger, J., B. Trollfors, E. Bergfors, N. Knutsson, V. Sundh, T. Lagergard, L. Lind-Brandberg, G. Zackrisson, J. White, H. Cicirello, J. Fusco, and J. Robbins. 2001. Mass vaccination of children with pertussis toxoid-decreased incidence in both vaccinated and nonvaccinated persons. Clin. Infect. Dis. 33: 1004–1010.
- van Baalen, M., and M. Sabelis. 1995. The dynamics of multiple infection and the evolution of viruelence. Am. Nat. 146: 881–910.
- Veiga-Fernandes, H., U. Walter, C. Bourgeois, A. McLean, and B. Rocha. 2000. Response of naive and memory CD8+ T cells to antigen stimulation in vivo. Nat. Immunol. 1: 47–53.
- Vitetta, E., M. Berton, C. Burger, M. Kepron, W. Lee, and X. Yin. 1991. Memory B and T cells. Annu. Rev. Immunol. 9: 193–217.
