Antiviral protection following immunization correlates with humoral but not cell-mediated immunity

Smallpox was a deadly disease when it was rife yet despite its eradication more than 30 years ago, the possibility of accidental or intentional release has driven research in search of better definitions of correlates of protective immunity. Mousepox, a disease caused by ectromelia virus (ECTV), is arguably one of the best surrogate small animal models for smallpox. Correlates of protection in mousepox are well defined during primary infection, whereas those in a secondary infection, which have definite relevance to vaccination strategies, are less well understood. We previously established that neutralizing antibody (Ab), which is generated far more rapidly during a secondary infection compared with a primary infection, has a key role during a secondary virus challenge. In this study, we show that the route of immunization or the use of homologous or heterologous virus vaccines for immunization does not influence the ability of mice to control high-dose virulent ECTV challenge or to mount a substantial secondary neutralizing Ab response. In contrast, the recall cytotoxic T lymphocyte (CTL) responses generated under these regimes of immunization were varied and did not correlate with virus control. Furthermore, unlike the recall Ab response that was generated rapidly, the kinetics of the secondary antiviral CTL response was no different to a primary infection and peaked only at day 8 post-challenge. This finding further underscores the importance of Ab in conferring protection during secondary poxvirus infection. This information could potentially prove useful in the design of safer and more efficacious vaccines against poxviruses or other diseases using poxvirus vectors.