Biology Reference
In-Depth Information
found to elicit CD8
+
T lymphocyte responses and, following boost with inactivated
MCMV, high levels of virus-neutralizing antibody. Following MCMV challenge,
titers of virus were either at or below the detection limits for the salivary glands,
liver, and spleen of most immunized animals (Morello et al. 2005). These results
support further study of prime-boost approaches for vaccination in other animal
models, and, potentially, for future clinical trials of HCMV vaccines.
Perspectives
Although it is appropriate to consider multiple potential options for HCMV
vaccination, the principle barrier to licensure of a vaccine is not a paucity of accept-
able candidate vaccines from which to currently choose. Rather, the major barrier
to progress is the lack of knowledge about the public health significance of con-
genital HCMV infection and the disabilities it produces in children. Increased pub-
lic awareness about the risks of HCMV is urgently needed: this in turn will drive
the social, political, and economic forces necessary to increase the pace of progress
of clinical trials. Vaccine manufacturers need to increase emphasis on research and
development of novel strategies at the same time that clinical trials of existing can-
didates move forward.
Although it has been asserted that a better understanding of the correlates of
protective immunity must be achieved before the goal of a HCMV vaccine can
be realized, in fact licensure and implementation of any of the vaccines tested to
date would likely impact significantly on disease. A recent analysis by the
Cannon group at the CDC examined the force of infection of HCMV, defined as
the instantaneous per capita rate of acquisition of infection that approximates the
incidence of infection in the seronegative population. Among individuals of
reproductive age in the United States, the force of infection was 1.6 infections
per 100 susceptible persons per year. Comparison of this to the basic reproduc-
tive rate of 1.7 indicated that, on average, an infected person transmits CMV to
nearly two susceptible people - a relatively low force of infection when compared
to other vaccine-preventable infectious diseases (Colugnati et al. 2007). This
analysis suggested that even a modestly effective vaccine and rate of vaccination
compliance could significantly reduce CMV transmission. Sterilizing immunity
conferred by a vaccine is therefore not likely to be necessary for prevention of
disease and disability in newborns due to congenital HCMV infection. Indeed,
insights from the GPCMV model of congenital infection suggest that reduction
of viral load below a critical threshold, and not sterilizing immunity, is sufficient
to ensure improved pregnancy outcomes following vaccination in the setting of
maternal viremia. Therefore, the pace of research should be substantially acceler-
ated with existing vaccine candidates, even as research continues to more fully
explore the correlates of protective immunity. Although expensive to perform
and logistically challenging to conduct, it is imperative that trials be powered to
examine symptomatic congenital HCMV infection as an efficacy endpoint.
