The focus of WHO’s World Immunisation Week is closing the immunisation gap, which means getting vaccines that already exist to those who need them. But there are many diseases for which we do not have a vaccine, or the vaccine we have is not effective enough.
Dr Charlie Weller, who leads Wellcome's vaccines work, highlights some of these infections, and why developing a safe and effective vaccine is particularly challenging.
Most of us take vaccines for granted. We are used to getting regular injections when we are children and teenagers, and occasionally when we go abroad.
But, we still lack vaccines to many of the most common infectious diseases, not to mention emerging infections and neglected tropical diseases.
Vaccines work by mimicking our body’s natural response to an infection so that the next time we are exposed, our immune system knows how to respond and protect us against disease.
The steps to developing a vaccine are similar across all diseases, but each comes with its own specific challenges. Here are seven infectious diseases for which vaccine development has proved a tough nut to crack.
HIV hides inside the immune system,infecting the very cells that are needed to coordinate a response against the virus. Many years and billions of dollars have been invested in developing an HIV vaccine. Some hope came in 2009, with a vaccine which protected 31% of people. Researchers are trying to understand what parts of the immune response protected those people, so that they can design better vaccines. In a promising development, researchers have recently found antibodies that completely block HIV from infecting cells and are racing to design vaccines that recreate them.
Unlike diseases caused by viruses or bacteria, malaria is caused by a tiny parasite with a complex life cycle. After more than 25 years in development, at a cost of over $800m, the first malaria vaccine was licensed in 2015. However, the RTS,S vaccine was less effective than many hoped – protecting only around a quarter to a half of children. Still, as malaria is responsible for over 500,000 deaths every year, RTS,S is still a huge breakthrough that could save many lives. We now need to figure out how best to use this new vaccine in combination with bed nets, mosquito control and other approaches.
More than half a million children under five die each year from rotavirus infections. Most of these happen in developing countries, where getting existing vaccines to those who need them is problematic for many reasons including what’s called the ‘cold chain’. Vaccines are very sensitive to temperature and must be transported from the manufacturer to the patient in a series of fridges or freezers stretching across the world. In rural areas or those prone to power cuts, up to half of vaccine doses are ‘spoilt’ because the cold chain is broken or faulty. Making existing vaccines more tolerant to heat and freezing would reduce waste and increase access to life-saving vaccines. Work by the Wellcome-funded Hilleman labs in India is underway to achieve this for rotavirus.
The BCG vaccine has been used for over 90 years. It protects against more severe forms of TB, but is not effective against pulmonary TB (in the lungs). One third of the world’s population is estimated to be infected with TB, but not everyone who carries the bacterium will get sick. Finding out why is crucial to designing a more effective vaccine. The need has never been more pressing, with resistance to TB drugs on the rise around the world. People with TB must take daily antibiotics for up to nine months, but many stop taking them earlier contributing to the problem of drug resistance. The situation is so bad that there are now people with TB who cannot be cured.
Chagas is caused by a parasite Trypanosoma cruzithat infects humans through the bite of a blood-sucking bug. It is found mainly across Latin America in some of the poorest communities. Like malaria, T cruziparasites have evolved to hide from the human immune system. One approach is a therapeutic vaccine – given to people already infected to ‘boost’ their immune system to eliminate the parasite once and for all. However, vaccine development is expensive, and for this complicated disease which affects mainly those who can’t pay for a vaccine, the field is lagging behind.
Flu is a seasonal illness, and each new season brings with it a slightly different form of the virus. This means a new flu jab must be made each year to match the circulating strains that experts have predicted are most likely to become a problem. A big worry is that it can take six months to make the first doses, so if a flu virus changes and suddenly becomes very deadly (pandemic flu), it might take many months before enough vaccine can be made to protect everyone.
Researchers are trying to create a ‘universal’ flu vaccine, which would provide lifelong protection from all strains of the virus. But this is a long way off. In the meantime, the WHO is helping countries to increase their manufacturing capacity so they are ready to produce as much vaccine as possible in the event of a pandemic.
Zika has rarely been out of the headlines since the beginning of 2016. This mosquito-transmitted disease is in the same family as dengue, chikungunya and yellow fever. At the start of the current epidemic in South America, no vaccine candidates existed. However, Zika vaccine development is progressing rapidly, including one approach that uses the dengue vaccine as a ‘backbone’. As the dengue vaccine has already been shown to be safe in people, this approach may speed up development.
An added complication of Zika vaccines is that the people most in need of protection are pregnant women or women thinking of becoming pregnant. These women are usually initially excluded from clinical trials, so we must figure out the safest but quickest way to ensure a vaccine gets to them.