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.