A TEAM OF UCT researchers at a critical phase of developing a plant-based prophylactic vaccine against human papillomaviruses (HPVs), responsible for the high rates of cervical cancer in Africa, have received a welcome R1.2-million grant from the Poliomyelitis Research Foundation (PRF). The PRF is the premier African foundation funding virology research.
The researchers will use the funds (R400 000 a year for three years) to conduct further research towards final HPV vaccines. Their pioneering work, started with a previous PRF grant and continued with funding from the Department of Arts, Culture, Science and Technology (DACST) Innovation Fund, has already gathered one United States and three preliminary South African patents.
Specific types of HPV are causally associated with cervical cancer, the second most common cancer among South African women. Although cervical screening programmes have resulted in a drop in the number of cervical cancer cases in the developed world, this is not the case in Africa. In most parts of the continent, the only hope of reducing the disease is a successful HPV vaccination programme.
"We have gone a long way to making novel papillomavirus vaccines, which would, if successful, go a long way to lessening the impact of cervical cancer," said a "seriously chuffed" Professor Ed Rybicki of the Plant-Based Vaccines Group in the Department of Molecular and Cell Biology, who heads the team. Rybicki's co-applicant, and wife, is Professor Anna-Lise Williamson (Division of Medical Virology), the remainder of the team consisting of postdoctoral student Dr Inga Becker, PhD students Arvind Varsani and Thomas Kohl, and technician Juliet Hogg.
"The grant also constitutes valuable recognition of what has become a very productive team effort between a group of researchers from the Science and Health Sciences Faculties, grouped under the new Institute of Infectious Disease and Molecular Medicine (IIDMM), of which Professor Williamson and myself are members," Rybicki added.
One of the group's challenges is to produce HPV vaccines that are novel and, of course, cost as little as possible to produce. "Our aim is both to continue developing HPV vaccines as well as to develop novel protein and DNA-based approaches," he explained.
Broadly, the team is refining and improving HPV types 11 and 16 L1or major capsid protein-based virus-like particle (VLP) vaccines produced in plants. They are also attempting to develop novel HPV-16 and –11 L1 and L2 chimaeric virus-like particles (VLPs), expressing additional group-specific antibody-binding and CTL-inducing determinants. In addition, they are developing DNA vaccines for HPVs 11 and 16 L1 capsid and other non-capsid proteins.
"The HPV vaccines presently undergoing human trials are peptide vaccines, subunit vaccines such as virus-like particles (VLPs) or recombinant vaccinia virus. In Africa we need a safe, effective vaccine that is cheap to produce. With the exception of the poxvirus-based vaccines, none of the present vaccines undergoing human trials satisfy all these criteria," Rybicki said.
The best candidate protein for a prophylactic vaccine against HPV is the major capsid protein L1 which "self-assembles" into virus-like particles (VLPs). According to Rybicki, these VLPs are mainly produced in insect cells via baculovirus expression systems and are very well characterised. "The injection of VLPs produced from the capsid proteins of HPVs into experimental animals induces neutralising antibodies. Preliminary human trials of injected VLP vaccines have also shown that these are well tolerated and highly immunogenic, and in the former case, stimulate robust B and T cell responses."
A novel recent approach that holds great promise (it was partially pioneered in the team's laboratories) is mucosal immunisation with HPV VLPs by oral administration. "An exciting new field in vaccine development is the use of proteins made in transgenic plants as edible or oral vaccines in order to induce mucosal immunity in human," Rybicki said. "Vaccine proteins can also often be more effectively produced in plants by means of plant viral vectors, as they produce much more protein than transgenic plants."
The strategy for immunisation against pathogens that affect mucosal surfaces relies on the fact that higher vertebrates have a common mucosal immune system. "This means that immunity induced in the gut will give immunity at other mucosal sites, including the respiratory and urogenital tracts. Our aim is to use plant-produced VLPs for the oral immunisation of people against HPV, to protect against mucosal infection."
(Note: The IIDMM is currently involved in a national and international fundraising campaign to generate capital to refurbish facilities for the new Institute.)