The recombinant vaccines are highly effective and safe, and have helped set the standard for later introductions, such as of the recombinant VLP-based Human papillomavirus (HPV) vaccines. While this was initially still expensive – US$40/dose, with three intramuscular doses being necessary – prices have come down very significantly, to the point that more than 110 countries now routinely immunise infants as part of the Extended Programme of Immunisation (EPI).

It was a triumph of modern molecular biology, therefore, when a very similar virus-like particle (VLP) vaccine derived from expression of the HBV small surface antigen (S-HBsAg) was developed in 1984. However, this was in the form of 22 nm subviral particles purified from the serum of human carriers of HBV, and although highly effective, was expensive to produce and of limited supply – to say nothing of the ever-present risk associated with a blood product isolated from HBV carriers who may carry any number of other, as yet undetected viruses. Hepatitis B virus (HBV) vaccines are one of the blockbuster vaccine success stories of modern times: since identification of the virus in the 1960s, it took less than 20 years for a subunit vaccine to get to market. This review will cover the relevant recent history of virus-specific candidate vaccines and virus-specific therapeutic antibodies made in plants, with a view to providing object examples of successful approaches and especially of dual human/animal use or “One Health” examples ( ), in order to help inform future work. Aspects of this history have been covered recently, and in particular for virus-like particle based vaccines including rotaviruses and Norwalk virus, Human papillomaviruses and Hepatitis B virus, and so these will not be discussed in detail here except where there is new material to be covered. Virus vaccines have been a large and exciting part of this field almost from its beginning, for disease agents ranging from Hepatitis B to C to Foot and mouth disease viruses, from Human papillomavirus and Human rotavirus to ovine Bluetongue and Rabbit haemorrhagic disease viruses, to mention just a few. Over the years since 1989, then, many proteins have been expressed as candidate vaccines or therapeutics, and many different plant-based expression systems have been tried, with a growing trend towards transient expression systems based on infiltration of whole plants with recombinant Agrobacterium tumefaciens (agroinfiltration) and the use of “deconstructed” plant viral vectors (reviewed in ).

However, this concept has now largely fallen out of favour, with the realisation that administration of vaccines to humans requires standardisation of dose and some measure of quality control, and the necessity for purification and formulation has largely been accepted. Initially, the prevailing idea for the use of plant-produced vaccines was that these should be delivered in plant material, as edible vaccines – something that was already being questioned as early as 1996.

Egg based vaccine production