VACCINES

Since the onset of the dreaded COVID-19 pandemic, a vaccine against the disease has arguably become one of the most talked about topics in 2020 and 2021. With the introduction of the newly developed COVID-19 vaccines around the world, and their impending roll-out in Australia in early 2021, we felt it timely to deep-dive into the very interesting, and much debated, topic of vaccines.

Dr Danielle Stanisic and Dr Reshma Nevagi, who both work within our Laboratory of Vaccines for the Developing World here at the Institute for Glycomics, give us an introductory overview on vaccines.  These impressive female research scientists are currently working on a world-first whole parasite blood-stage malaria vaccine candidate which is in human clinical trials. Malaria is one of the world’s most deadly diseases, infecting over 200 million people worldwide, and claiming nearly half a million lives each year. Their malaria vaccine candidate, if proven safe and effective in clinical trials, could quite literally save millions of lives.

For the next few minutes, these immunology experts take us on a journey into the subject of their everyday life…vaccines.

Let’s start with the basics. What is a vaccine?

A vaccine is a biological product that activates the body’s immune system to protect against infection and/or disease. There are 2 main types of vaccines (i) Prophylactic (preventative) vaccines that aim to prevent infection and (ii) Therapeutic vaccines which are used for treatment and may target non-infectious diseases e.g. cancer.

There are many different types of vaccine but they can be broadly classified as live or non-live vaccines.  Live vaccines contain a weakened form of the relevant pathogen whereas non-live vaccines contain either an inactivated form of the pathogen or components of the pathogen.

What types of pathogens are vaccines effective against?

Vaccines are effective against many different organisms.  These include:

• viruses – e.g. influenza virus, varicella-zoster virus (chickenpox), human papillomavirus (HPV), mumps virus, polio virus and hepatitis B virus
• bacteria – e.g. the bacteria that cause meningitis, tetanus, tuberculosis and pertussis).  
• parasites – vaccines are also being developed for parasitic diseases e.g. malaria and hookworm infections.  

How do vaccines work to prevent infection by pathogens?

An effective vaccine safely trains the immune system to recognise and fight pathogens e.g. viruses or bacteria. 

Our body recognises the vaccine components as ‘foreign’, similar to what happens during an actual infection with the bacteria or virus, and this activates and trains cells of the immune system (e.g. B cells and T cells).  In this way, the immune system safely learns to recognise and combat the pathogen that the vaccine is targeting. 

Following vaccination, if a person is subsequently exposed to the pathogen, the immune system remembers and kills it before it can cause disease.

What is in a vaccine?

A vaccine’s main component is a whole or partial version of the specific pathogen that the vaccine is targeting.  Some vaccines also contain substances known as adjuvants, which are chemicals that enhance the immune response and improve the vaccine’s effectiveness.  A vaccine may also contain preservatives to prevent bacterial/fungal contamination and to ensure that it is safe to administer. 

Can you explain what is meant by a ‘sub-unit’ vaccine?

A sub-unit vaccine is a non-live vaccine that contains one or more components (antigens) derived from the pathogen of interest.  These may be directly derived from the pathogen of interest or made synthetically.

These antigens are typically selected based on their critical biological function; for example, they contribute to the pathogen’s ability to cause disease or they contribute to its entry into, or survival within, the human body.  

Sub-unit vaccines generally include an adjuvant to enhance the immune response against the antigen component of the vaccine. 

The hepatitis B vaccine is an example of a sub-unit vaccine.

In contrast to a sub-unit vaccine, what is a whole organism vaccine?

A whole organism vaccine contains the entire pathogen, either in an killed or live, attenuated (weakened) form.   

For a killed vaccine, the pathogen is inactivated by heat or chemical treatment. Killed whole organism vaccines often include an adjuvant.  The inactivated polio vaccine is an example of a killed whole organism vaccine.

A live, attenuated vaccine contains a weakened form of the pathogen whose disease-causing potential (or virulence) has been reduced e.g. by treatment with chemicals, radiation or a specific genetic mutation.  Live, attenuated, replicating vaccines should not be given to people with an impaired immune system. The measles, mumps, rubella (MMR) vaccine is an example of a live, attenuated whole organism vaccine.

Can you give some examples of how vaccination has proven effective against some of the world’s most harmful diseases?

The smallpox vaccine is the ultimate vaccine success story.  In the 1790s, Edward Jenner first demonstrated that injection with the benign cowpox virus resulted in protective immunity against a similar virus which caused the deadly disease known as smallpox. 

Centuries later, the smallpox vaccine was used in mass global vaccination campaigns and smallpox was eventually declared eradicated by the World Health Organization (WHO) in 1980.  

Many other vaccines are administered today and are highly effective.  These include measles, mumps, rubella, chickenpox, tetanus, diphtheria and polio vaccines. Vaccines that have been more recently developed and approved include the hepatitis B vaccine and the human papillomavirus vaccine. According to the WHO, there are 23 diseases/pathogens for which vaccines are available (link).

What is herd immunity?

Unfortunately, vaccines cannot protect everybody directly as there is a proportion of the population who either cannot be immunised for different reasons (e.g. they are too young, they have an impaired immune system), or who do not develop a protective immune response following vaccination. 

If the vaccine prevents infection and if enough people in the population are immunised, it is possible that these unimmunised individuals can be protected through ‘herd immunity’.  Once herd immunity is achieved, the pathogen cannot easily spread in the community and susceptible individuals are ‘protected’ indirectly.  Herd immunity can effectively limit or stop the spread of the disease in the community.

The percentage of individuals within a population that needs to be immunised to achieve herd  immunity differs for each disease and is based on how infectious the pathogen is and how effective the vaccine is.  For highly infectious pathogens (e.g. the virus that causes measles), a higher percentage of the population needs to be immunised compared with less infectious pathogens.  If immunisation rates fall below this threshold, then herd immunity breaks down and disease outbreaks can occur. 

Is vaccination safe?

Extensive safety testing is required for all vaccines before they are approved for use in Australia and other countries around the world.  Once vaccines are approved and are routinely used, they continue to be monitored for safety.  

Short-term side effects after vaccination e.g. redness, swelling and pain at the site of vaccination and mild fever can occur;  however, they are usually mild and do not require special treatment.  Serious reactions are extremely rare.  Although vaccines can present side effects in some people, their benefits in preventing severe disease and death greatly outweigh the risks.  Possible side effects of a vaccine are explained by the vaccination provider e.g. your doctor, prior to receiving the vaccine.

Are there any downsides to vaccination?

• Vaccines are made with different components, and if someone is allergic to one or more of those components, it could trigger an allergic reaction.  This occurs in a very small number of people and it affects their ability to be successfully immunised.  This is why vaccines are administered under the supervision of trained medical staff. 
• Minor side-effects may also occur, but these are normally short-lived. 
• It is possible that a person may still get sick even if they have been vaccinated.  For example, this is sometimes seen with the current seasonal influenza vaccines. 
• A proportion of the population may not be well enough to be vaccinated, for example their immune systems are weakened, or they cannot be successfully immunised due to other factors. 

It’s important to remember, however, that the benefits of vaccination greatly outweigh the risks.  Vaccines protect both you and the people around you who may not be well enough or are not able to be vaccinated.  

Are all vaccines designed to be preventative; are there any vaccines that work as therapeutics?

The majority of vaccines that are currently used are preventative; that is, they are designed to train the immune system to fight against infection with new pathogens in the future. 

There are also therapeutic vaccines, which are administered to stimulate the immune system to fight harder against an existing infection or disease.  Currently approved therapeutic vaccines include those used in cancer treatment and the post-exposure rabies vaccine.  There are also a number of experimental therapeutic vaccines which target other non-infectious diseases e.g. diseases of the immune system and Alzheimer’s disease.

Sometimes we hear the term ‘vaccine candidate’. Can you explain the terms ‘vaccine candidate’ and ‘vaccine’

The term ‘vaccine candidate’ is typically used while a vaccine is undergoing development and it is being evaluated for safety and efficacy against the disease it is targeting.  There may be many different vaccine candidates being developed for a single disease.  If the testing is successful and the vaccine candidate is shown to be safe and effective, it may then be approved for use by the different regulatory agencies e.g. the US Food and Drug Administration (FDA) and Australia’s Therapeutic Goods Administration (TGA) and licensed.  Once it is licensed, the term ‘vaccine’ is used.

Generally, how long does it take to create a vaccine?

Vaccine development is a long process.  Developing a new vaccine typically takes between 10-15 years from the initial laboratory-based studies, through the various phases of clinical trials, to the final approval of the vaccine.  

How much does it cost to develop a vaccine?

Developing a vaccine is both time-consuming and expensive. Although the cost to develop a vaccine varies, in general it’s estimated to cost anywhere from US$500 million to US$1 billion.

What is the process that needs to be taken to progress a vaccine candidate from the discovery phase to being readily available to the public?

The development and evaluation of a vaccine candidate follows a standard set of steps before it can be approved for use. 

Initially pre-clinical laboratory studies are conducted.  This can involve laboratory models, where available, to optimise the vaccine candidate to improve its effectiveness and to demonstrate that it is safe.  Once safety has been demonstrated in pre-clinical studies, it then progresses through three phases of clinical trials in humans. 

Phase I trials involve a small number of healthy adults (25-100), with the primary aim of evaluating safety and identifying minor side effects.  The ability of the vaccine candidate to stimulate an immune response (immunogenicity) may also be examined. 

If it is shown to be safe in Phase I trials, it progresses into Phase II trials and is administered to hundreds of adults to further examine safety, immunogenicity and any side effects.  Vaccine efficacy may also be examined. 

In Phase III trials, the vaccine is given to thousands of people to test whether it can protect against the target disease and to identify any rare or serious side effects.  In these studies, the effectiveness of the vaccine candidate may be compared against a placebo vaccine (an unrelated vaccine) or an already approved vaccine for the same disease.  

The data generated during this process is then evaluated by the appropriate regulatory agencies e.g. the US Food and Drug Administration (FDA) and Australia’s Therapeutic Goods Administration (TGA), who decide if it can be approved and registered for use. 

Following approval, Phase IV studies involve the continued collection of data on vaccine effectiveness and safety over a longer period of time.

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