Vaccine technologies: From whole organisms to rationally designed protein assemblies

Abstract

Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development.

Next generation immunology: the quest for a universal vaccine

“…For example, innate immune cells engulf pathogens, secrete cytokines that promote inflammation and release chemicals that attract and activate other immune cells. 1 The adaptive immune system responds to specific areas in the infected cell or pathogen called 'epitopes'. The adaptive immune system has two elements: humoral and cellular.…”

“…For example, when a receptor expressed by a B lymphocyte binds to a matching epitope, it matures into a plasma cell that secretes antibodies -the humoral response. 1 "The body's immune system functions via different mechanisms depending on the route of infection," Dr Fjällman says. "An injectable vaccine nicely mimics an insect bite, for example, while an oral vaccine might be more appropriate for a mucosal pathogen."…”

“…Their mechanism of action -which is, according to a recent review, "not completely understood and still widely debated" -probably depends on the vaccine, route of administration and organism. 1 Broadly, aluminium seems to stimulate innate immune cells at the site of vaccination. In particular, aluminium seems to attract immature dendritic cells, which then mature and present the vaccine to T-helper cells in lymph nodes.…”

“…In turn, these T-helper cells stimulate B cells that encounter the vaccine to generate high titres of antibodies. 1 Nevertheless, safety concerns surround some adjuvants. Aluminium-based adjuvants have been associated with macrophagic myofasciitis, for example.…”

“…Vaccination is also responsible for the only two infections wiped out by human innovation -smallpox in 1979 and the livestock disease rinderpest in 2011 -and has brought measles and polio to the verge of extinction. 1 Nevertheless, there is a pressing need for innovative immunisations, although finding new vaccines is increasingly difficult. "We've picked the low-hanging fruit," says Georgina Drury, programme manager for immunology at the UK MRC's Infections and Immunity Board.…”