Viral Vector Vaccine

A viral vector vaccine uses a harmless or weakened carrier virus, often an adenovirus, that has been genetically engineered to carry the gene for a target antigen. After vaccination the vector enters cells and delivers these instructions, so the recipient's own cells transiently produce the antigen, eliciting both antibody and T-cell responses. Vectors may be replication-deficient or replication-competent, and pre-existing immunity to the carrier virus is a recognised design consideration.

Definition

A viral vector vaccine is an immunising preparation in which a non-pathogenic or attenuated carrier virus is engineered to deliver a gene encoding a target antigen, so that the vaccinated person's cells transiently express that antigen and mount a protective immune response.

Scope

This entry covers how a carrier virus is engineered to deliver an antigen gene, the immune responses the platform elicits, and design considerations such as vector choice and anti-vector immunity. It is a platform-level reference within vaccine types and does not provide schedules, dosing, or individual immunisation advice.

Core questions

• How is a carrier virus engineered to deliver an antigen gene without causing its own disease?
• Why do viral-vector vaccines tend to elicit strong T-cell as well as antibody responses?
• How does pre-existing immunity to the vector influence platform design and choice of carrier?
• What distinguishes replication-deficient from replication-competent vector approaches?

Key concepts

• Carrier (vector) virus
• Antigen-encoding transgene
• In situ antigen expression
• Antibody and T-cell responses
• Replication-deficient vs replication-competent vectors
• Pre-existing anti-vector immunity
• Heterologous prime-boost

Mechanisms

A carrier virus is modified to remove or disable genes needed for disease and to insert the gene for the chosen antigen. After administration the vector infects cells and delivers the transgene, which the cell transcribes and translates into the antigen; because the antigen is produced inside cells and the vector itself engages innate immune sensing, the platform characteristically induces both antibody responses and strong T-cell immunity. Replication-deficient vectors deliver a single round of expression, while replication-competent vectors can amplify the signal. A recognised limitation is pre-existing immunity to the carrier virus, which can blunt responses; this is mitigated by selecting rare or non-human vectors or by using different vectors in a heterologous prime-boost.

Clinical relevance

Viral-vector vaccines reached large-scale human use during the COVID-19 pandemic, where randomised trials supported the efficacy of adenovirus-vectored products, and the platform has also been used in outbreak settings for other diseases. This entry describes how the platform works and how it generates immunity; it is not a basis for individual immunisation decisions, which follow current schedules and official guidance.

Evidence & guidelines

Randomised controlled trials supported the efficacy of adenovirus-vectored COVID-19 vaccines, and the platform's antigen presentation and mode of action are compared with other platforms in vaccinology reviews. Product-specific recommendations are issued by the World Health Organization and national immunisation advisory bodies.

History

Engineering viruses as gene-delivery vectors grew out of recombinant DNA and gene-transfer research, and adenovirus and other vectors were developed as vaccine platforms over several decades. The approach reached its widest clinical deployment during the COVID-19 pandemic with adenovirus-vectored vaccines and had earlier been applied in outbreak responses to other pathogens.

Key figures

• Sarah Gilbert
• Andrew Pollard

Seminal works

• voysey-2021
• bos-2020
• heinz-stiasny-2021

Frequently asked questions

Does the carrier virus in a viral vector vaccine cause infection?

No. The carrier virus is engineered to be harmless or unable to replicate in the recipient; it serves only to deliver the gene for the target antigen so the body can produce that antigen and respond to it.

Why does pre-existing immunity to the vector matter?

If a person already has immunity to the carrier virus, that immunity can neutralise the vector and weaken the response, which is why designers may use rare or non-human vectors or combine different vectors in a prime-boost approach.