Preclinical evidence for implementing a prime-boost vaccine strategy for tuberculosis

Abstract

In this review, published peer-reviewed preclinical studies using prime-boost tuberculosis (TB) vaccine regimens in animal challenge models for tuberculosis have been evaluated. These studies have been divided into groups that describe prime-boost vaccine combinations that performed better than, equivalent to, or worse than the currently used BCG vaccine. Review of the data has revealed interesting findings, including that more than half of the published studies using BCG as a prime combined with a novel boost vaccine give better efficacy than BCG alone and that the greatest reduction in Mycobacterium tuberculosis (M.tb.) colonization of animal tissues is provided by viral vectored vaccines delivered intranasally. Careful evaluation of these data should assist in defining the value of prime-boost regimens for advancement into human TB vaccine trials and stimulate the development of criteria for choosing which vaccine candidates should be studied further.

Figure 1. Log reduction of CFU provided by prime-boost vaccine compared with BCG alone. (See Table 1A vaccines.)

Prime-boost combinations that protect better than BCG alone. Certain investigational TB vaccines reduce the colonization of lungs (A) and spleens (B) when used to immunize animals previously primed with BCG vaccines and then challenged with virulent strains of M.tb. Data is taken from the studies described in Table 1A that include CFU data from lungs and spleen compared with a BCG vaccine control. Experiments where protection by BCG alone was ≤ 0.3 log10 CFU reduction are indicated by an asterisk (*). Statistical analyses were not performed for this set of data due to the lack of access to raw data in certain studies. * Indicates experiments where protection from BCG alone was ≤ 0.3 log10 CFU reduction.