Cross-strain protection reduces effectiveness of virally vectored fertility control: results from individual-based multistrain models

Pest mammals have severe economic, environmental and social impacts throughout the world. Fertility control could reduce these impacts. Virally vectored immunocontraception (VVIC) has been proposed as an economic way to achieve this. However, the ability of an immunocontraceptive virus to control populations may be compromised if: (i) sufficient infected mice are not made infertile; (ii) the virus does not transmit at a sufficient rate; (iii) there is competition with field strains of virus; or (iv) its ability to induce infertility is altered by the presence of field strains. We tested this with stochastic, individual-based, disease-host models based on murine cytomegalovirus (MCMV) and house mice Mus musculus domesticus. Using field estimates of the MCMV transmission rate, immunocontraceptive MCMV (icMCMV) could prevent mouse populations from growing rapidly to damaging levels provided > 70% of mice infected with the virus became infertile. Successful control was possible even if engineering icMCMV reduced its transmission rate to c. 30% of the field-estimated value, but greater reductions in the transmission rate compromised successful control. Effective control was compromised if there was competition between icMCMV and field strains because of cross-immunity to infection or if previous infection with field strains blocked the development of infertility in mice subsequently infected with icMCMV. In these cases effectiveness was diminished, particularly if the transmission rate of icMCMV was reduced relative to field strains, or if close to 100% infertility of infected mice could not be achieved. If the blocking developed early after infection with field strains, doubling the transmission rate of icMCMV relative to field strains still could not produce successful control. Synthesis and applications. VVIC requires preliminary estimates of its efficacy to satisfy regulatory requirements before it can be released into the environment. Our models indicate that successful control of an outbreaking species using VVIC is possible if high levels of infertility can be achieved, but this is compromised by cross-strain protection and low transmission rates of engineered virus. Future research effort should focus on determining whether these compromising effects occur for specific engineered viruses and, if so, whether they can be overcome.