Transmissible Viral Vaccines

Abstract

Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution. Approaches that integrate vaccine engineering with an understanding of evolution and epidemiology will reap the greatest benefit from vaccine transmission.

Keywords: epidemiology; genome engineering; herd immunity; population dynamics; vaccine evolution.

Figure 1

Key    Figure: Basic Epidemiological Properties of Transmissible Vaccines Each row represents a population at a point in time. Time flows down. Gray circles are individuals with the vaccine, open circles are susceptible. Arrows represent transmission of the vaccine from one individual to another. Directly vaccinated individuals are those with no arrow leading into them. (A) A weakly transmissible vaccine. Direct vaccination occurs in the first time interval shown, and the vaccine quickly dies out. (B) A highly transmissible vaccine; the vaccine spreads. (C) A weakly transmissible vaccine in which direct vaccination continues throughout the time shown. Although chains of transmission are short, they increase the number of vaccinated individuals within the population.

Figure 2

A Transmissible Vaccine That Occasionally Reverts to Its Wild-Type State. (A) A weakly transmissible attenuated vaccine that reverts. The revertants (red) have high transmissibility, but are suppressed by ongoing vaccination. (B) A highly transmissible recombinant vector vaccine that reverts – loses its antigenic insert (blue). Revertants are also blocked by ongoing vaccination, provided the complete vaccine elicits immunity against both the pathogen and vector.