An update on vaccines for COVID-19

Written by Dr David Owens

Updated on May 31th, 2021

COVID-19 has resulted in an ’infodemic’ which has been subject to both misinformation and disinformation. It is likely that the roll out of vaccines will see an increase in disinformation. We have undertaken a survey of vaccine perceptions in our population which showed high levels of vaccine acceptance in OT&P patients in comparison to the relatively low levels in the Hong Kong population. The single greatest factor in vaccine hesitancy is worry over vaccine safety. This is understandable and appropriate. Open and honest communication of evolving risk benefit will be key to increasing vaccine uptake. We will continue to update this page as we accumulate data.

The Hong Kong Government has announced the procurement of three different vaccine candidates which will be dependent upon peer reviewed evidence from ongoing studies. This makes perfect sense. Voluntary immunization programs rely upon trust in Health institutions. The distribution of all COVID-19 vaccines will be managed via the government. The government has now given emergency licensing approval to both Pfizer-BioNTech and Sinovac Biotech vaccines and vaccination for both vaccines has started. Vaccinations are being given in both government centres and within private medical clinics that have registered for the vaccination subsidy scheme. We are long term members of this scheme and will be involved in the vaccination process. At present OT&P and all private clinics are ONLY able to give Sinovac vaccines. In anticipation of managing what will invariably be a logistical challenge, we have undertaken significant IT development. The impact of the vaccination program on the population will be maximised if vaccinations can be given in an equitable manner based upon clinical need. This will be dependent on age, occupational and clinical risk. The health department has announced that the program will be voluntary and individuals will be able to choose which vaccine they wish to take. The details of the government program can be found here.

The following vaccinations have been sourced by the Hong Kong government:

1. The Pfizer-BioNTech vaccine: This is an mRNA vaccine. It represents a new technology in which a small segment of mRNA is injected into the body. This causes the body to produce spike protein and leads to the development of immunity. This vaccine (along with the Moderna vaccine which is also mRNA) report the highest efficacy rates^[1]. It has been given emergency licensing approval by a number of countries. This is a new technology and safety and efficacy data has recently been published in the New England Journal of Medicine^[2]. Vaccination involves 2 shots 21 days apart. In Hong Kong the data sheet for the vaccine given can be found here.
2. Sinovac Biotech: This is a more traditional inactivated vaccine. The phase 1 and 2 trials were reported in the Lancet^[3]. The phase 3 trials are due to report shortly. This vaccine will be able to be stored in a standard fridge making widespread use easier than the mRNA vaccines. It is given as 2 shots 28 days apart. Initial press reports suggested that the vaccine had been used extensively with good evidence of efficacy. The Hong Kong expert committee announced efficacy of 62.3% when approving the vaccine for emergency use. It is difficult to make accurate comparisons until all trial data is available. The summary of the scientific committee findings reported to the CHP are available here.
3. Oxford-AstraZeneca: This is a viral vector vaccine using an engineered adenovirus. The phase 3 studies have been reported in the Lancet showing efficacy between 62 - 90% depending upon the dose^[4].The lower initial dose produced a better response. More recently studies in the UK have also shown higher response when the second shot was delayed to 12 weeks. This finding supports the UK decision to delay the second dose. The vaccine is currently recommended to be given as 2 shots 28 days part although this may change as increasing data becomes available. AstraZeneca vaccine can be stored in a standard fridge and the company is running the project as a not-for-profit. This vaccine is likely to be used widely in developing nations.

Over the last few weeks further vaccines have been reported to have acceptable levels of efficacy. Both Novovax and Johnson and Johnson vaccines showed lower effectiveness over the South Africa variant than other sub types. This trend has been noted with a number of vaccines and is certainly a reason for caution regarding evolving mutations. We will update the situation as reliable data evolves.

The table below summarises the current available evidence for different COVID-19 vaccines.

Developing a COVID-19 Vaccine

The development of the COVID-19 vaccine candidates has occurred at an unprecedented rate. There is still much that we do not know^[5]. Normally vaccines develop through three phases of trials. These trials are mostly designed to answer a couple of questions.

1. Is the vaccine safe?
2. Is the vaccine effective in preventing disease and/or reducing disease severity?

The vaccine trials for COVID-19 have been powered to identify a reduction in disease. These studies are very expensive to undertake and typically recruit around 30,000 volunteers. They are designed to complete if they identify around 150 cases. The cases are confirmed by PCR testing but they are generally symptomatic, mostly mildly symptomatic although there have been some more serious disease. Regardless, the studies show the vaccine candidates to be generally safe within the numbers involved and to show effectiveness in reducing cases of illness. It will be important to analyse the final reported phase 3 trials closely. Studies with different end points (clinical severe, moderate, mild and asymptomatic disease) will produce different values. The studies all have slightly different methods and headline numbers such as 95% Pfizer versus 50% Sinovac are not necessarily comparing like with like. This article describes the dilemmas and common pitfalls of interpreting vaccine trials^[6].

There are other questions which the phase 3 trials are not necessarily able to answer yet. The questions which require further ongoing research include:

1. Is the vaccine effective in reducing or preventing transmission of the virus?
2. How long is the vaccine effective and will booster doses be required?
3. How does the vaccine behave in different populations?

Reducing the likelihood of an individual developing severe illness is obviously very important. All the vaccines are very effective at preventing death and serious disease. Only with greater data will we understand whether the vaccines also reduce transmission and asymptomatic infections. We are now accumulating more data to suggest that this is the case. In particular data from Israel and the UK suggests significant reduction in infections as well as reduction in severe disease. This will be important in increasing the effectiveness of vaccination in controlling the epidemic.

Much more data is necessary in order to identify rarer complications, although we have now given many millions of doses and so this data is accumulating. We also need longer term studies in order to fully understand the length of immunity and the need for boosters. Finally, we need to better understand the effectiveness of the vaccines in different populations including differences of age and ethnicity.

The development of vaccine candidates represents an incredible scientific achievement. The new mRNA vaccines in particular represent an enormous leap in vaccine development in terms of management of current and future infectious disease. If they work as well as some of the early data suggests and challenges to distribution and storage can be overcome, then we may genuinely be seeing one of the great medical advances of our lifetime. However, we are still early in the process and more data is required. A recent editorial in the Lancet Microbe is entitled COVID-19: The Pandemic will not end overnight^[7]. There are many other vaccine candidates in different stages of research. The World Health Organisation keeps an updated list of vaccines under development^[8]. As we accumulate more data it may be that other vaccines may offer advantages in terms of safety, effectiveness or in the ability to impact the spread of the disease in addition to reducing disease severity. Understanding the different factors will require continued research and surveillance.

We will continue to update this page as further evidence is published.

Reference

1. Moderna's COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study. (n.d.). Retrieved December 14, 2020, from https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy
2. Polack, F., Al., E., For the C4591001 Clinical Trial Group*, Author AffiliationsFrom Fundacion INFANT (F.P.P.) and iTrials-Hospital Militar Central (G.P.M.), Longo, E., F. P. Polack and Others, . . . E. J. Rubin and D. L. Longo. (2020, December 10). Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine: NEJM. Retrieved December 21, 2020, from https://www.nejm.org/doi/10.1056/NEJMoa2034577
3. Safety, tolerability, and immunogenicity of an inactivated ... (n.d.). Retrieved December 14, 2020, from https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext

4. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine ... (n.d.). Retrieved December 15, 2020, from https://www.thelancet.com/lancet/article/s0140-6736(20)32661-1

5. Doshi, P. (2020, October 21). Will covid-19 vaccines save lives? Current trials aren't designed to tell us. Retrieved December 15, 2020, from https://www.bmj.com/content/371/bmj.m4037
6. New Vaccine Data Is Coming: Watch Out for These 3 Claims​​​​​​​ (n.d.). Retrieved January 22, 2021, from https://www.wired.com/story/new-vaccine-data-is-coming-watch-out-for-these-3-claims/ 
7. COVID-19 vaccines: The pandemic will not end overnight ... (n.d.). Retrieved December 21, 2020, from https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30226-3/fulltext
8. Draft landscape of COVID-19 candidate vaccines. (n.d.). Retrieved December 15, 2020, from https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines