Impact of cross-protective vaccines on epidemiological and evolutionary dynamics of influenza

Abstract

Large-scale immunization has profoundly impacted control of many infectious diseases such as measles and smallpox because of the ability of vaccination campaigns to maintain long-term herd immunity and, hence, indirect protection of the unvaccinated. In the case of human influenza, such potential benefits of mass vaccination have so far proved elusive. The central difficulty is a considerable viral capacity for immune escape; new pandemic variants, as well as viral escape mutants in seasonal influenza, compromise the buildup of herd immunity from natural infection or deployment of current vaccines. Consequently, most current influenza vaccination programs focus mainly on protection of specific risk groups, rather than mass prophylactic protection. Here, we use epidemiological models to show that emerging vaccine technologies, aimed at broad-spectrum protection, could qualitatively alter this picture. We demonstrate that sustained immunization with such vaccines could-through potentially lowering transmission rates and improving herd immunity-significantly moderate both influenza pandemic and seasonal epidemics. More subtly, phylodynamic models indicate that widespread cross-protective immunization could slow the antigenic evolution of seasonal influenza; these effects have profound implications for a transition to mass vaccination strategies against human influenza, and for the management of antigenically variable viruses in general.

The beneficial effects of vaccination on the evolution of seasonal influenza

“…Universal vaccines that immunize against all strains necessarily slow antigenic evolution by not discriminating between antigenic variants [12]. However, despite the fact that conventional vaccines create selective gradients among antigenic variants, our results suggest that conventional vaccines still reduce evolution and drive extinction.…”

“…Universal vaccines, which confer immunity against all antigenic variants, slow antigenic evolution by uniformly decreasing the fitness of all strains [12]. Conventional vaccines against seasonal influenza, which confer narrower immunity, might also slow antigenic evolution.…”

“…In theory, seasonal influenza vaccines could slow antigenic evolution [10][11][12][13]. Universal vaccines, which confer immunity against all antigenic variants, slow antigenic evolution by uniformly decreasing the fitness of all strains [12].…”

Navigating the Devious Course of Evolution: The Importance of Mechanistic Models for Identifying Eco-Evolutionary Dynamics in Nature

“…For our parameterization, this calculation indicates that the benefit of vaccination extends beyond simply decreasing the number of currently infected hosts; vaccination has the additional effect of reducing the rate of antigenic evolution. This result is echoed in a recent study that found that a broad-spectrum influenza vaccine could potentially decrease the rate of antigenic evolution as well as decrease disease incidence (Arinaminpathy et al 2012). Because peaks in incidence occur in years with strain turnover ( fig.…”

Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

“…Thus, annual vaccine reformulation is necessary to ultimately maintain immunity against seasonal influenza viruses [4,5]. Furthermore, antigenic drift renders uniform population wide vaccination campaigns, that have led to the control of measles and smallpox, ineffective for influenza virus [6]. Clearly, there is a great need for a vaccine that induces heterosubtypic protection against all influenza A viruses.…”