Recombinant transmissible vaccines will be intrinsically contained despite the ability to superinfect

ABSTRACT

Introduction

Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses – Lassa, Ebola, rabies. To ensure safety, current designs propose a recombinant vector platform in which the vector is isolated from the target wildlife population. Because using an endemic vector creates the potential for preexisting immunity to block vaccine transmission, these designs focus on vector viruses capable of superinfection, spreading throughout the host population following vaccination of few individuals.

Areas covered

We present original theoretical arguments that, regardless of its R₀ value, a recombinant vaccine using a superinfecting vector is not expected to expand its active infection coverage when released into a wildlife population that already carries the vector. However, if superinfection occurs at a high rate such that individuals are repeatedly infected throughout their lives, the immunity footprint in the population can be high despite a low incidence of active vaccine infections. Yet we provide reasons that the above expectation is optimistic.

Expert Opinion

High vaccine coverage will typically require repeated releases or release into a population lacking the vector, but careful attention to vector choice and vaccine engineering should also help improve transmissible vaccine utility.

KEYWORDS:

• Vaccine
• transmission
• mathematical model
• population biology
• evolution
• recombinant

Article highlights

• Transmissible vaccines for wildlife could block zoonoses with minimal investment.

• Proposed vaccine designs use a recombinant platform with a vector that can superinfect to overcome host immunity and an antigenic insert against the target pathogen. Safety dictates that the vaccine be released into the host population from which the vector was obtained.

• We show that vaccines using these designs are, under the most ideal conditions for vaccine spread, expected to maintain a constant level of active infections in the host population.

• A vaccine is expected to decline if it cannot infect or transmit from hosts immune to the pathogen or if the antigenic insert interferes with vaccine transmission.

• Even with a low active vaccine presence, a vaccine can create a large immunity footprint in the population if it repeatedly superinfects hosts; superinfection rates are unknown, so it is not clear if a large immunity footprint is attainable.

• On balance, transmissible vaccine success will require careful choice of vector and vaccine engineering. Ongoing vaccine releases are likely to be needed to maintain vaccine presence.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

All data in this study are numbers generated by iteration of equations given in the supplements and displayed in the figures. Initial conditions for these numerical trials are given in the figures. As such, the data are fully reproducible from the information provided.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2024.2320845

Additional information

Funding

This paper was initiated in anticipation of a March 2023 workshop on transmissible vaccines supported by NSF DEB 2216790; discussions at that meeting further motivated many of the arguments herein. M Griffiths is supported by Wellcome Trust grant 217221/Z/19/Z to DG Streicker, SL Nuismer by grants NIH 2R01GM122079-05A1 and NSF DEB 2314616. R Antia was supported by the National Institutes of Health grants U01 AI150747 and U01 AI144616.