English physician Edward Jenner developed the first vaccine more than 200 years ago to protect against smallpox. It was needle-free, involving arm-to-arm inoculation with the vaccinia virus.
Vaccinology as a discipline and a public health intervention developed exponentially in the mid 20th century. Vaccines against diphtheria, tetanus, whooping cough and polio were the first to have a major impact on disease burden globally.
But as more vaccines are developed, the challenge of delivering them with minimal pain, anxiety and number of visits to the doctor has increased.
How to vaccines work?
Immunisation is based on the principle that presenting the body with a part of a microorganism (or a similar structure) can induce a protective immune response.
The body’s response to infection includes the skin and underlying tissue, which are rich with various immune cells that can stimulate an immune response. That’s why most vaccines are administered into the muscle or skin tissues, and require a needle for delivery.
Some, however, such as the oral polio vaccine are a live attenuated virus, administered as oral drops, which then stimulate an immune response in the immune cells of the gut.
Pain and fear
Research from Toronto shows that 24% of parents and 63% of children reported fear of needles; resulting in about 7% of children not getting vaccines when recommended.
A recent study from the United States found that about 38% of parents were concerned about the pain from receiving so many shots.
HPV vaccine is delivered in New Zealand schools but a number of girls who sign up for vaccine do not receive the full three doses– fear of needles could be one of main reasons for the drop off.
One strategy to reduce needles has been to combine several vaccines into one shot. Even so, infants and toddlers still require several shots to complete the recommended schedule. So new needle-free technologies offer an additional solution.
Nanopatches
Developed by Mark Kendall at the University of Queensland, the nanopatch involves a 1cm square of silicone with 20,000 vaccine-coated microprojections on the surface which penetrate the skin and deliver the vaccine painlessly.
The product is currently in the development phase, and is being tested with different vaccines.
Nasal spray vaccines
The nasal spray flu vaccine (also called the live attenuated influenza vaccine) is exactly what it sounds like – a spray you inhale to protect against seasonal influenza.
The nasal spray flu vaccine has been approved in some developed countries but is not available for use in Australia.
Recently, an inhalable Ebola vaccine has been developed. It shows promising results in primates, and confirms that immunity to Ebola can be conferred through the respiratory tract.
Dry powder vaccines
Dry powder vaccines that are inhaled into the lungs are effective in initiating immune responses.
They have been found to fight infections in a similar way to injectable vaccinations, but have fewer side effects.
Oral vaccines
Oral vaccines are administered directly to the gastrointestinal system to induce local immunity in the lining of the gut and stimulate the immune system to fight some bacteria and viruses.
Vaccines against polio, rotavirus and cholera are commonly administered orally.
Pharmajet
The company Pharmajet has developed a needle-free injector for the influenza vaccine with Australian pharmaceutical company Seqirus. It uses a high pressure injector device which delivers the vaccine into the skin without a needle.
The rate of local side effects (such as redness and pain after vaccination), however, has been reported to be higher than standard injections.
Pharmajet injectors are available for use in the United States, but not in Australia.
Sugar microneedles
Researchers in the United Kindom have developed a sugar disc with multiple microneedles containing dried live virus vaccine, which deliver the vaccine into the skin without a needle. Preliminary testing of this device is promising.
Edible vaccines
Edible vaccines are being developed, where the vaccine is delivered on an edible platform which could range from bacteria to plants. The latter includes transgenic crops, which overcome problems of vaccine storage within the cold chain, which constrain the use of traditional vaccines in low-resource settings.
Which vaccines to choose?
Improving the experience of vaccination will almost certainly have a positive impact on vaccination programs. Needleless devices will also reduce the risk of needle-stick injuries to health-care workers.
But the choice of needles versus needle-free vaccines must also be guided by other considerations. Most importantly, needle-free vaccines must be as good or better at preventing disease.
Other considerations include cost, production capacity (and ability to supply large population vaccine programs), storage conditions (such as temperature control), and side effects. These must all be considered and weighed up to ensure maximal individual and public health benefit of vaccines.
As newer vaccines become available and disease prevention targets increase, needle-free technology will become increasingly attractive.
C Raina MacIntyre receives funding from The National Health and Medical Research Council and Australian Research Council. In the past she has received funding or in-kind support for investigator-driven research, or been on advisory boards for vaccine manufacturers Merck, GSK, Pfizer and BiCSL. She is on influenza and pneumococcal working parties for the Australian Technical Advisory Group on Immunisation.
Daniel Salmon has received served as a consultant and/or received research funding from Merck, Crucell, Parents of Kids with Infectious Diseases (PKIDS), and US federal government agencies and philanthropic organizations.
Elizabeth Kpozehouen’s position is partly funded by NHMRC.