Covid vaccine could be conserved by excluding the already infected

The approval of Moderna's Covid-19 vaccine by the European Medicine Agency (EMA) on Wednesday is very welcome news amid the very worrying rise in number of cases of SARS-CoV-2 infections and hospitalisations with Covid-19 in Ireland.

The Government travel restrictions have not prevented importation of SARS-CoV-2, especially the more transmissible variants from the United Kingdom and South Africa. Early data suggests that current vaccine may protect against these variants.

The initial objective of the vaccination programme must be to protect the vulnerable from hospitalisation and deaths from Covid-19. The residents in long-term care facilities, frontline healthcare workers and the older general population are the top priority. More than 90 per cent of deaths from the virus in Ireland have been in individuals over 65.

Under the supply agreement between the European Union and the vaccine manufacturers, Ireland is expected to receive just more than 4 million doses of the Pfizer and Moderna vaccines, enough to immunise about 2 million people with a two-dose schedule.

Inside an Irish ICU: ‘We are nowhere near the Covid-19 peak’

---

More than 200 Covid-19 related deaths in North at height of Christmas holiday

---

Millions of Covid-19 vaccine doses to be available monthly in second half of year

---

Covid-19: Almost all private hospitals agree to take public patients

---

There are more than 600,000 people in Ireland over 65 and, adding 250,000 healthcare workers, residents in long-term care facilities and people with underlying medical conditions, including 225,000 with diabetes, the most vulnerable population in Ireland is well more than 1 million, which will require over 2 million doses of vaccine. A further 2 million doses will be required for 45- to 65-year-olds.

However, the incidence of the virus in Ireland is highest in individuals between 15 and 44 years, who are at the bottom on the priority list for vaccination. While the implementation of the vaccination programme should reduce deaths from the virus within a few months, it will have more limited immediate impact on transmission of SARS-CoV-2 in the general population.

More than 70 per cent of the population, including older children, will need to be immunised to achieve population or herd immunity and thereby prevent transmission of the virus.

There is great frustration with the pace of vaccine rollout, particularly since it is more advanced in the UK and Israel.

While Ireland is constrained – and facilitated – by the centralised EU agreements with the vaccine manufacturers, the biggest issue with rollout of the programme is vaccine supply.

Vaccine production requires complex manufacturing techniques and facilities. Even the Pfizer and Moderna mRNA vaccines, which are made using the most advanced technologies, are not trivial to produce in the billions of doses required to meet the global demand.

Additional vaccines from other pharmaceutical companies will help to ease the supply issue, but not immediately and there are some uncertainties.

The Oxford/AstraZeneca vaccine, which has the advantage of being stable for many months at fridge temperature, was authorised for emergency use by the UK regulatory agency, the Medicines and Healthcare Products Regulatory Agency, on the December 30th, 2020.

Ireland is due to get 3.3 million doses of this vaccine though the EU supply agreement. However, the EMA has stated that it requires additional information to rigorously assess quality, safety and efficacy of this vaccine.

Other Covid-19 vaccines from Johnson & Johnson, CureVac and Novavax are expected to report phase 3 clinical trial data in the coming months. The EU has advance purchase agreements that would see Ireland allocated 2.2 million and 2.45 million doses of J&J and CureVac vaccines respectively.

The Novavax vaccine, which is based on more tried and tested technology of a viral subunit (protein) with an immune enhancer (adjuvant), generated very high levels of virus-neutralising antibodies and protected against infection as well as disease in preclinical studies. However, the EU has yet to conclude a deal on supply of this vaccine.

One approach to conserve vaccine stocks, championed by the UK, is to delay administration of the second dose of vaccine, thus vaccination a larger number of people with a single dose.

There is some merit in this approach, especially for the younger population but not in the high-risk or older individuals.

Immune responses tend to be stronger with a longer interval between primary and secondary vaccination. However, there is limited data from the various clinical trials to suggest that one dose of a Covid-19 vaccine will confer high levels of protection. Immune responses generally drop off quickly after a single immunization with non-replicating vaccines.

An alternative approach is to prioritise vaccination for those who have not been infected with SARS-CoV-2, at least in the short term while vaccine supply is limited. People who have recovered from infection may not need to be vaccinated because they have already generated a protective immune response to the virus.

A study on healthcare workers in Oxford, published last week in the New England Journal of Medicine, showed that only two workers out of 1,265 that had previous confirmed SARS-CoV-2 infection became re-infected and both were asymptomatic, whereas there were 223 infections among 11,364 workers that had not previously been infected with SARS-CoV-2.

This study suggests that natural infection confers 100 per cent protection against Covid-19 disease and also gives very good protection against SARS-CoV-2 infection.

There are other documented cases of individuals becoming re-infected with SARS-CoV-2, but these are a tiny minority among the nearly 100 million confirmed cases of Covid-19 worldwide.

There have been nearly 128,000 PCR-confirmed cases of Covid-19 in Ireland. Based on current trends, we could have 300,000 cases six weeks from now. Vaccine stocks could be conserved by excluding these previously infected individual from the initial vaccination programme.

Close contacts of known cases are currently not being tested in Ireland; this allows asymptomatic individuals to go undetected and these can account for 40-50 per cent of all SARS-CoV-2 infections. Although mass serological testing of the population would be logistically challenging, it would allow identification of individuals who had asymptomatic infections, most of whom are known to develop antibodies. Although less clear cut than the confirmed PCR-positive cases, it might allow exclusion of another cohort from later rounds of vaccination.

It might be argued that we do not know if antibodies prevent re-infection with SARS-CoV-2 or if they persist for long periods after infection. However, the scientific evidence from the recent New England Journal of Medicine report and studies on other pathogens suggest that antibodies do protect against viral infections, and can persist for months or years.

If antibodies levels do decline to low levels, immune cells, called memory T and B cells should persist and confer more prolonged protection. Therefore, natural immunity should be exploited against a virus that is out of control; at least until vaccine supply is no longer an issue.

Kingston Mills is professor of experimental immunology and academic director of the Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland