On the role of cross-immunity and vaccines on the survival of less fit flu-strains

A pathogen’s route to survival involves various mechanisms including its ability to invade (host’s susceptibility) and its reproductive success within an invaded host (‘‘infectiousness’’). The immunological history of an individual often plays an important role in reducing host susceptibility or it helps the host mount a faster immunological response de facto reducing infectiousness. The cross-immunity generated by prior infections to influenza A strains from the same subtype provide a significant example. The results of this paper are based on the analytical study of a two-strain epidemic model that incorporates host isolation (during primary infection) and crossimmunity to study the role of invasion mediated cross-immunity in a population where a precursor related strain (within the same subtype, i.e. H3N2, H1N1) has already become established. An uncertainty and sensitivity analysis is carried out on the ability of the invading strain to survive for given cross-immunity levels. Our findings indicate that it is possible to support coexistence even in the case when invading strains are ‘‘unfit’’, that is, when the basic reproduction number of the invading strain is less than one. However, such scenarios are possible only in the presence of isolation. That is, appropriate increments in isolation rates and weak cross-immunity can facilitate the survival of less fit strains. The development of ‘‘flu’’ vaccines that minimally enhance herd cross-immunity levels may, by increasing genotype diversity, help facilitate the generation and survival of novel strains.

The current vaccination strategy targeted at people at highest risk of severe disease outcome is suboptimal because current vaccines are poorly immunogenic in these population groups.  Our results suggest that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (>70%) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning population immunity.

References:

• G. Chowell, M.A. Miller, C. Viboud. Seasonal influenza in the United States, France and Australia: Transmission and prospects for control. Epidemiology and Infection 2007 Jul 18;:1-13(pdf)
• M. Nuno, G. Chowell, X. Wang, C. Castillo-Chavez. On the role of cross-immunity and vaccination in the survival of less-fit flu strains.Theor. Pop. Biol. 71, 20-29 (2007) (pdf)

 

Fig. 1. Flow chart of the state progression of individuals in a population exposed to two influenza strains. Fully susceptible individuals (S) can become infected (primary infection) with Strain 1 (I1) or Strain 2 (I2). Infected individuals with Strain 1 (Strain 2) may become isolated Q1 (Q2) or recovered R1 (R2). Recovered individuals become infected (secondary infection) with Strain 1 (V1) or Strain 2 (V2). Infected individuals recover from both strains into class W.

Fig. 2. Summarized statistics for invasion reproduction number for varying levels of cross-immunity. The likelihood of coexistence, sub-threshold coexistence and no coexistence are illustrated for varying levels of cross-immunity. Parameters used in these calculations are provided in Table 1 with the exception of s12 (which varies between 0 and 1).