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Identifying the Conditions Under Which Antibodies Protect Against Infection by Equine Infectious Anemia Virus.

Schwartz EJ, Smith RJ - Vaccines (Basel) (2014)

Bottom Line: A more complete understanding is needed of antibody protection against lentivirus infection, as well as the role of mutation in resistance to an antibody vaccine.In addition, a three-strain competition model is considered in which a second mutant strain may coexist with the first mutant strain.The conditions that permit viral escape by the mutant strains are determined, as are the effects of variation in the model parameters.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences and Department of Mathematics, Washington State University, Pullman, WA 99164, USA. ejs@wsu.edu.

ABSTRACT
The ability to predict the conditions under which antibodies protect against viral infection would transform our approach to vaccine development. A more complete understanding is needed of antibody protection against lentivirus infection, as well as the role of mutation in resistance to an antibody vaccine. Recently, an example of antibody-mediated vaccine protection has been shown via passive transfer of neutralizing antibodies before equine infectious anemia virus (EIAV) infection of horses with severe combined immunodeficiency (SCID). Viral dynamic modeling of antibody protection from EIAV infection in SCID horses may lead to insights into the mechanisms of control of infection by antibody vaccination. In this work, such a model is constructed in conjunction with data from EIAV infection of SCID horses to gain insights into multiple strain competition in the presence of antibody control. Conditions are determined under which wild-type infection is eradicated with the antibody vaccine. In addition, a three-strain competition model is considered in which a second mutant strain may coexist with the first mutant strain. The conditions that permit viral escape by the mutant strains are determined, as are the effects of variation in the model parameters. This work extends the current understanding of competition and antibody control in lentiviral infection, which may provide insights into the development of vaccines that stimulate the immune system to control infection effectively.

No MeSH data available.


Related in: MedlinePlus

Viral persistence landscape diagram as Mutant 2 varies, showing that an increase in the mutation rate of Mutant 2 can stabilize the Mutant 1 equilibrium. The bistability region is included for completeness, but corresponds to unreasonably high mutation rates. Note the log scale on the axes.
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vaccines-02-00397-f001: Viral persistence landscape diagram as Mutant 2 varies, showing that an increase in the mutation rate of Mutant 2 can stabilize the Mutant 1 equilibrium. The bistability region is included for completeness, but corresponds to unreasonably high mutation rates. Note the log scale on the axes.

Mentions: Figure 1 illustrates the potential outcomes of viral strain persistence given the ranges of Mutant 2 growth and mutation rates. Note that rMj > dMj for j = 1, 2, so that the line R2 = 1 is an upper bound. Since the growth rate of Mutant 1 is assumed to exceed that of Mutant 2, it follows that the Mutant 2 equilibrium is always unstable (see Condition (1) in Appendix B). All parameters other than rM2 and ϵ2 are set to their sample values in Table 1, with m = 1. For , RE1 > 1 and RE3 > 1, so all three strains coexist. As ϵ2 increases, the Mutant 1 equilibrium becomes stable, so Mutant 1 persists. See Appendix B.1 for details.


Identifying the Conditions Under Which Antibodies Protect Against Infection by Equine Infectious Anemia Virus.

Schwartz EJ, Smith RJ - Vaccines (Basel) (2014)

Viral persistence landscape diagram as Mutant 2 varies, showing that an increase in the mutation rate of Mutant 2 can stabilize the Mutant 1 equilibrium. The bistability region is included for completeness, but corresponds to unreasonably high mutation rates. Note the log scale on the axes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494265&req=5

vaccines-02-00397-f001: Viral persistence landscape diagram as Mutant 2 varies, showing that an increase in the mutation rate of Mutant 2 can stabilize the Mutant 1 equilibrium. The bistability region is included for completeness, but corresponds to unreasonably high mutation rates. Note the log scale on the axes.
Mentions: Figure 1 illustrates the potential outcomes of viral strain persistence given the ranges of Mutant 2 growth and mutation rates. Note that rMj > dMj for j = 1, 2, so that the line R2 = 1 is an upper bound. Since the growth rate of Mutant 1 is assumed to exceed that of Mutant 2, it follows that the Mutant 2 equilibrium is always unstable (see Condition (1) in Appendix B). All parameters other than rM2 and ϵ2 are set to their sample values in Table 1, with m = 1. For , RE1 > 1 and RE3 > 1, so all three strains coexist. As ϵ2 increases, the Mutant 1 equilibrium becomes stable, so Mutant 1 persists. See Appendix B.1 for details.

Bottom Line: A more complete understanding is needed of antibody protection against lentivirus infection, as well as the role of mutation in resistance to an antibody vaccine.In addition, a three-strain competition model is considered in which a second mutant strain may coexist with the first mutant strain.The conditions that permit viral escape by the mutant strains are determined, as are the effects of variation in the model parameters.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences and Department of Mathematics, Washington State University, Pullman, WA 99164, USA. ejs@wsu.edu.

ABSTRACT
The ability to predict the conditions under which antibodies protect against viral infection would transform our approach to vaccine development. A more complete understanding is needed of antibody protection against lentivirus infection, as well as the role of mutation in resistance to an antibody vaccine. Recently, an example of antibody-mediated vaccine protection has been shown via passive transfer of neutralizing antibodies before equine infectious anemia virus (EIAV) infection of horses with severe combined immunodeficiency (SCID). Viral dynamic modeling of antibody protection from EIAV infection in SCID horses may lead to insights into the mechanisms of control of infection by antibody vaccination. In this work, such a model is constructed in conjunction with data from EIAV infection of SCID horses to gain insights into multiple strain competition in the presence of antibody control. Conditions are determined under which wild-type infection is eradicated with the antibody vaccine. In addition, a three-strain competition model is considered in which a second mutant strain may coexist with the first mutant strain. The conditions that permit viral escape by the mutant strains are determined, as are the effects of variation in the model parameters. This work extends the current understanding of competition and antibody control in lentiviral infection, which may provide insights into the development of vaccines that stimulate the immune system to control infection effectively.

No MeSH data available.


Related in: MedlinePlus