Vaccine-associated enhanced disease (VAED)

SARS CoV-2 (COVID-19) is an infection associated with a wide variety of symptoms and severity. This ranges from asymptomatic infection to severe acute respiratory distress, which can be fatal particularly in vulnerable populations. Given the severity and widespread fatality rate worldwide, developing a safe and effective vaccine is a global priority. This has lead to fast tracking the development of a SARS CoV-2 vaccine and a pathway for a provisional approval process using preliminary data. What would normally take 10-15 years to develop a vaccine, has been reduced to less than 12-months. This is due to a variety of factors including unprecedented financial investments and scientific collaborations, the use of vaccine platforms which have already been used in the development of other vaccines or new technologies, and the ability to run various steps of the research and development in parallel.

The introduction of any new vaccine requires close safety monitoring. The safety, immunogenicity and efficacy of SARS-CoV-2 must be carefully evaluated and an understanding of any potential serious adverse event which may arise, including disease enhancement, is vital to ensure vaccine acceptance and confidence.

What is it?

Vaccine-associated enhanced disease (VAED) occurs when an individual who has received a vaccine, develops a more severe presentation of that disease when subsequently exposed to that virus, compared with when infection occurs without prior vaccination.  This assumes that the vaccine recipient has not previously been exposed to the disease and is seronegative at time of immunisation.

The potential for vaccination with a SARS-CoV-2 vaccine to be associated with enhanced disease after subsequent infection is a theoretical risk, and the vaccine-induced antibody (so called antibody dependent enhancement) or TH1 biased  T-cell responses leading to adverse responses to natural SARS-CoV-2 infection need to be carefully evaluated once a COVID-19 vaccine rollout commences.

Background

Disease enhancement has previously been associated with dengue virus infection and was previously observed in humans with inactivated whole-virus vaccines against respiratory syncytial virus (RSV) and measles virus in the 1960s [refer to Science Translational Medicine: Prospects for a safe COVID-19 vaccine].

Previous animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV have also been shown to induce a more serious disease when subsequently exposed to the virus.

Current situation

Due to this theoretical concern, animal models of SARS-CoV-2 infection and preliminary data from phase I, II and III human trials of various COVID-19 vaccine candidates, have been closely monitored to measure specific cell subtypes (CD4 and CD8 T-cells) and the shift in Th1 to a Th2 CD4 T-cell response which can indicate increased risk of VAED. Clinical trials to date have not shown evidence of VAED after immunisation.

Assessment and evaluation

It can be difficult to distinguish between vaccine-failure (also known as breakthrough disease) and VAED. Identification of a case of VAED requires the recognition that a clinical presentation is different, atypical, modified or more severe in comparison to the natural disease presentation. Many factors need to be considered when making the assessment, including background rates, age, gender, time post vaccination, duration of disease, clinical course and progression and comorbidities (additional medical conditions). Various laboratory and clinical diagnostic parameters can be used to help assess the possibility of VAED, including detailed review of all cases of possible vaccine failure (i.e. severe disease presentations despite completion of the required doses of a SAR- CoV-2 vaccine).

What to do if concerned

If you are concerned regarding a case of possible VAED please contact your local vaccine safety service.

If you are in Victoria, please contact SAEFVIC on 1300 882 924 (option 1) or alternatively report online HERE.

The Melbourne Vaccine Education Centre (MVEC) will provide up-to-date information on VAED as it comes to hand via our COVID-19 FAQs reference page.

Resources

Authors: Nigel Crawford (Director SAEFVIC, Murdoch Children’s Research Institute), Adele Harris (SAEFVIC Research Nurse, Murdoch Children's Research Institute) and Georgina Lewis (SAEFVIC Clinical Manager, Murdoch Children's Research Institute)

Date: January 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Vaccine development and safety

Like any medication in development, vaccine candidates must undergo rigorous testing procedures and scientific evaluation to prove not only their effect on the targeted disease, but also to determine their safety, before being licensed and registered for use in vaccination programs. In Australia, the Therapeutic Goods Administration (TGA) is responsible for assessing vaccines and other medicines for use in Australia.

Once vaccines have been introduced into the community, the safety and effectiveness of vaccines then continues to be monitored in the post-licensure phase through active surveillance programs and further trials. This is to ensure that there are no issues that may have been missed during the development phase.

Development phase

During vaccine development, initial safety testing of a vaccine candidate occurs in two stages. Stage one involves preclinical assessment in the laboratory.  Stage two involves the evaluation of the vaccine candidate in three phases of clinical trials. If a vaccine candidate fails the safety tests performed in stage one, it cannot progress further into the stage two clinical trials.

Phase I clinical trials: the vaccine candidate is given to small numbers (25–50) of healthy adults with the primary goal of assessing safety.

Phase II clinical trials: If the vaccine candidate is found to be safe in Phase I, it is then given to hundreds of people to determine: how effectively it stimulates immune responses; to determine the optimal dose regimen; and whether there are any side effects.

Phase III clinical trials: If the vaccine candidate is found to be effective and safe in Phase I and II, it is then given to many thousands of people to test whether it protects large populations from the target disease and to determine if there are any uncommon or serious side effects.

A vaccine must pass all of these phases before it is registered for use by the TGA. Approval of vaccines can take up to 10 years.

Post-licensure phase

Despite the extensive safety testing undertaken before a vaccine is licensed, some side effects are so uncommon, they cannot be detected even after studying a vaccine in thousands of people. For this reason, post-licensure assessment is performed.

Safety and effectiveness continue to be monitored using a variety of mechanisms. These may include:

  • further clinical trials
  • surveillance of the impact of the vaccine on the disease it aims to prevent using networks such as PAEDS
  • surveillance of adverse events following immunisation using systems such as AusVaxSafety and reporting services like SAFEVAC and SAEFVIC

What happens if a problem is suspected?

Any suspected problem with a vaccine signals the need for a thorough investigation by the TGA.

If a suspected problem could be serious, authorities will consider a range of actions including suspending use of the vaccine during the investigation.

COVID-19 vaccine development process

COVID-19 vaccine development is happening faster than usual because of the global impact of the pandemic and the urgent need for a vaccine(s). It is important to note that a candidate COVID-19 vaccine(s) must pass through the same phases of clinical trials and hasn't missed any of the important steps. Approval will only be given if the vaccine meets the requirements for safety and efficacy.

Provisional registration can be granted using a formal pathway for speeding up the registration of a COVID-19 vaccine candidate using preliminary clinical data. The decision to grant provisional registration is based on a number of factors, and ensures that the safety, quality and effectiveness of the vaccine has been satisfactorily established for its intended use. Following provisional approval, the Therapeutic Goods Administration (TGA) will continue to closely monitor any new data about the vaccine as it becomes available [refer to MVEC: Provisional registration of COVID-19 vaccine(s) in Australia].

 

Resources

Authors: Georgina Lewis (Clinical Manager SAEFVIC, Murdoch Children's Research Institute) and Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute)

Reviewed by: Georgina Lewis (Clinical Manager SAEFVIC, Murdoch Children's Research Institute) and Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute)

Date: December 2020

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Victorian council immunisation sessions

Each local council throughout Victoria offers regular immunisation sessions for the administration of all funded National Immunisation Program (NIP) vaccines. Sessions are free to attend and people of all ages requiring NIP vaccines can be vaccinated. Sessions are run by accredited nurse immunisers with medical support. Some councils may also choose to have additional vaccines such as meningococcal (Nimenrix® or Bexsero®), influenza and chickenpox vaccines available for purchase for those who do not meet the eligibility criteria for funded vaccines [see resources]. All vaccines administered are recorded on the Australian Immunisation Register (AIR).

Please refer to the tables below for contact details of your local council to obtain further information regarding session times.

Metropolitan councils

Council Telephone number Immunisation sessions
Banyule City Council (03) 9490 4222 Banyule immunisation session times
Bayside City Council (03) 9599 4444 Bayside immunisation session times
Boroondara City Council (03) 9278 4444 Boroondara immunisation session times
Brimbank City Council (03) 9248 4000 Brimbank immunisation session times
Cardinia Shire Council 1300 787 624 Cardinia immunisation session times
City of Casey (03) 9705 5200 Casey immunisation session times
Darebin City Council (03) 8470 8562 Darebin immunisation session times
Frankston City Council 1300 322 322 Frankston immunisation session times
Glen Eira City Council (03) 9524 3333 Glen Eira immunisation session times
Greater Dandenong City Council (03) 8571 1000 Dandenong immunisation session times
Hobsons Bay City Council (03) 9932 1000 Hobsons Bay immunisation session times
Hume City Council (03) 9205 2200 Hume immunisation session times
Kingston City Council 1300 653 356 Kingston immunisation session times
Knox City Council (03) 9298 8000 Knox immunisation session times
Manningham City Council (03) 9840 9333 Manningham immunisation session times
Maribyrnong City Council (03) 9688 0145 Maribyrnong immunisation session times
Maroondah City Council (03) 9298 4598 Maroondah immunisation session times
Melbourne City Council (03) 9340 1451 Melbourne immunisation session times
Melton City Council (03) 9747 7200 Melton immunisation session times
Monash City Council (03) 9518 3555 Monash immunisation session times
Moonee Valley City Council (03) 9243 8888 Moonee Valley immunisation session times
Moreland City Council (03) 9240 1111 Moreland immunisation session times
Mornington Peninsula Shire (03) 5950 1000 Mornington immunisation session times
Nilumbik Shire Council (03) 9433 3111 Nilumbik immunisation session times
Port Phillip City Council (03) 9209 6383 Port Phillip immunisation session times
Stonnington City Council (03) 8290 1333 Stonnington immunisation session times
Whitehorse City Council (03) 9262 6197 Whitehorse immunisation session times
Whittlesea City Council (03) 9217 2170 Whittlesea immunisation session times
Wyndham City Council (03) 9742 0777 Wyndham immunisation session times
Yarra City Council (03) 9205 5555 Yarra City immunisation session times
Yarra Ranges Shire Council 1300 368 333 Yarra Ranges immunisation session times

Regional councils

Council Telephone number Immunisation sessions
Alpine Shire Council (03) 5755 0555 Alpine immunisation session times
Ararat Rural City Council (03) 5355 0200 Ararat immunisation session times
Ballarat City Council (03) 5320 5850 Ballarat immunisation session times
Bass Coast Shire Council (03) 5671 2211 Bass Coast immunisation session times
Baw Baw Shire Council (03) 5624 2411 Baw Baw immunisation session times
Benalla Rural City Council (03) 5760 2600 Benalla immunisation session times
Buloke Shire Council 1300 520 520 Buloke immunisation session times
Campaspe Shire Council (03) 5481 2200 Campaspe immunisation session times
Central Goldfields Shire Council (03) 5461 0610 Central Goldfields immunisation session times
Colac Otway Shire Council (03) 5232 9400 Colac-Otway immunisation session times
Corangamite Shire Council (03) 5232 7100 Corangamite immunisation session times
East Gippsland Shire Council (03) 5153 9500 East Gippsland immunisation session times
Gannawarra Shire Council (03) 5450 9333 Gannawarra immunisation session times
Glenelg Shire Council (03) 5522 2211 Glenelg immunisation session times
Golden Plains Shire Council (03) 5220 7111 Golden Plains immunisation session times
Greater Bendigo City Council (03) 5434 6000 Bendigo immunisation session times
City of Greater Geelong (03) 4215 6962 Geelong immunisation session times
Greater Shepparton City Council (03) 5832 9700 Shepparton immunisation session times
Hepburn Shire Council (03) 53482306 Hepburn immunisation session times
Hindmarsh Shire Council (03) 5391 4444 Hindmarsh immunisation session times
Horsham Rural City Council (03) 5382 9777 Horsham immunisation session times
Indigo Shire Council 1300 365 003 Indigo immunisation session times
Latrobe City Council 1300 367 700 Latrobe immunisation session times
Loddon Shire Council (03) 5494 1200 Loddon immunisation session times
Macedon Ranges Shire Council (03) 5422 0333 Macedon Ranges immunisation session times
Mansfield Shire Council (03) 5775 8555 Mansfield immunisation session times
Mildura Rural City Council (03) 5018 8100 Mildura immunisation session times
Mitchell Shire Council (03) 5734 6200 Mitchell immunisation session times
Moira Shire Council (03) 5871 9222 Moira immunisation session times
Moorabool Shire Council (03) 5366 7100 Moorabool immunisation session times
Mount Alexander Shire Council (03) 5472 1364 Mount Alexander immunisation session times
Moyne Shire Council 1300 656 564 Moyne immunisation session times
Murrindindi Shire Council (03) 5772 0333 Murrindindi immunisation session times
Northern Grampians Shire Council (03) 5358 8700 Northern Grampians immunisation session times
Pyrenees Shire Council (03) 5349 1100 Pyrenees immunisation session times
Borough of Queenscliffe Council (03) 5258 1377 Queenscliffe immunisation session times
South Gippsland Shire Council (03) 5662 9200 South Gippsland immunisation session times
Southern Grampians Shire Council (03) 5573 0444 Southern Grampians immunisation session times
Strathbogie Shire Council (03) 5795 0000 Strathbogie immunisation session times
Surf Coast Shire Council 1300 610 600 Surf Coast immunisation session times
Swan Hill Rural City Council (03) 5036 2333 Swan Hill immunisation session times
Towong Shire Council (02) 6071 5100 Towong immunisation session times
Rural City of Wangaratta (03) 5722 0888 Wangaratta immunisation session times
Warrnambool City Council (03) 5559 4855 Warrnambool immunisation session times
Wellington Shire Council 1300 366 244 Wellington immunisation session times
West Wimmera Shire Council (03) 5585 9900 West Wimmera immunisation session times
City of Wodonga (02) 6022 9300 Wodonga immunisation session times
Yarriambiack Shire Council (03) 5398 0100 Yarriambiack immunisation session times

For any feedback relating to this page please email us at info.mvec@mcri.edu.au

Resources

Author: Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children’s Research Institute)

Reviewed by: Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute)

Date: August 2020

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Vaccine hesitancy

At MVEC we strongly encourage people to seek answers to their questions and to be well informed with evidence based information. We know that nearly half of all parents have some concerns about immunising their children, ranging from minor concerns to more serious degrees of vaccine hesitancy.

There is a lot of information available to people, particularly on the internet, which can be quite overwhelming. However, we know that health care providers, particularly GPs, nurses and paediatricians, are the most frequently accessed resources for immunisation information for parents and the most trusted. We also know that providing information alone is not enough to address parents concerns about immunisation and we would encourage them to speak with their health care provider as well as accessing information from recommended websites or online.

MVEC is committed to providing up-to-date information to help address questions about immunisation, appreciating that this information needs to be in multiple formats and cover a broad range of queries.

Below is a selection of reliable resources that can help in the decision-making process.

Resources

Authors: Margie Danchin (Senior Research Fellow, Murdoch Children’s Research Institute) and Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute)

Reviewed by: Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children's Research Institute) and Margie Danchin (Senior Research Fellow, Murdoch Children’s Research Institute)

Date: March 2019

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Vaccine schedule by country

The World Health Organisation (WHO) has a summary website of immunisation schedules by region and country.

This is a very helpful resource when determining vaccine catch-up recommendations for overseas patients. In addition it can assist to determine immunisation recommendations for those traveling overseas.

To identify the routine vaccines in a specific country select it from the drop down list, select all vaccines and press ok.

Resources

Author: Rachael McGuire (Research Nurse, SAEFVIC, Murdoch Children's Research Institute)

Reviewed by: Rachael McGuire (Research Nurse, SAEFVIC, Murdoch Children's Research Institute))

Date: September 2020

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Varicella

What is it?

Varicella (chickenpox) is a highly contagious infection caused by the varicella-zoster virus (VZV).

What to look for

Infection usually begins with 1-2 days of fever, runny nose and lethargy.

An itchy rash follows, involving fluid filled vesicles (blisters) that can cover any part of the body including inside the mouth, eyelids and genital area. Severe complications can include pneumonia, meningitis and encephalitis.

Varicella in pregnancy can result in skin scarring, ocular anomalies, limb defects and neurological malformations for the infant.

The virus can be reactivated later in life and cause Zoster (Shingles).

How is it transmitted?

Varicella can be transmitted by coughing or sneezing, or from direct contact with the fluid inside the vesicles.

Prevention

Immunisation is the most effective form of prevention. A single dose of the live-attenuated vaccine is currently funded on the National Immunisation Program (NIP) for children at age 18 months of age, however giving a 2nd dose (not funded) provides greater protection. For those ≥ 14 years of age, 2 doses (administered 4 weeks apart) are required for the protection on non-immune individuals.

Post-exposure prophylaxis

If a non-immune individual is exposed to disease, immunisation is recommended within 3-5 days (provided immunisation is not contraindicated). This can reduce the likelihood of varicella infection developing.

Neonates (whose mother develops infection up to 7 days prior to delivery or within 2 days after delivery), infants < 1-month of age (if mother is seronegative), pregnant women, premature infants (while still hospitalised, regardless of maternal serology) or immunosuppressed individuals who are exposed to varicella disease should receive Zoster Immunoglobulin (ZIG).

Repeat doses of ZIG may be given if a person is exposed to varicella again > 3-weeks after the first dose of ZIG.

Resources

Author: Rachael McGuire (Research Nurse, SAEFVIC, Murdoch Children's Research Institute)

Reviewed by: Rachael McGuire (Research Nurse, SAEFVIC, Murdoch Children's Research Institute)

Date: July 2020

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family's personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.