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The approval of Moderna’s Covid-19 vaccine by the European Medical Agency (EMA) on Wednesday is very good news amid the very worrying increase in the number of cases of SARS-CoV-2 infections and hospitalizations with Covid-19 in Ireland.
Government travel restrictions have not stopped the importation of SARS-CoV-2, especially the more transmissible variants from the UK and South Africa. Early data suggests that the current vaccine may protect against these variants.
There is great frustration with the pace of vaccine rollout, especially as it is more advanced in the UK and Israel.
The initial goal of the vaccination program should be to protect vulnerable people from hospitalization and death from Covid-19. Residents of long-term care facilities, frontline healthcare workers and the general older population are the top priority. More than 90% of deaths from the virus in Ireland are in people over 65.
As part of the supply agreement between the European Union and vaccine manufacturers, Ireland is expected to receive just over 4 million doses of Pfizer and Moderna vaccines, enough to immunize around 2 million people with a two-dose schedule.
There are over 600,000 people in Ireland over the age of 65 and, adding 250,000 healthcare workers, residents of long-term care facilities and people with underlying health conditions, including 225,000 with diabetes, the population Ireland’s most vulnerable is well will require more than 2 million doses of vaccine. Two million additional doses will be needed for those 45 to 65 years old.
However, the incidence of the virus in Ireland is highest among people between 15 and 44 years old, who are low on the priority list for vaccination. While the implementation of the immunization program is expected to reduce deaths from the virus within a few months, it will have an immediate, more limited impact on the transmission of SARS-CoV-2 in the general population.
More than 70% of the population, including older children, will need to be vaccinated to achieve population or herd immunity and thus prevent transmission of the virus.
There is great frustration with the pace of vaccine rollout, especially as it is more advanced in the UK and Israel.
While Ireland is constrained – and facilitated – by the EU’s centralized agreements with vaccine makers, the biggest problem with the rollout of the program is vaccine supply.
The production of vaccines requires complex manufacturing techniques and facilities. Even the Pfizer and Moderna mRNA vaccines, which are manufactured using the most advanced technologies, are not trivial to produce in the billions of doses needed to meet global demand.
Additional vaccines from other pharmaceutical companies will help alleviate the supply problem, but not immediately and there are some uncertainties.
The Oxford / AstraZeneca vaccine, which has the advantage of being stable for many months at refrigerator temperature, has been urgently authorized by the UK regulatory agency, the Medicines and Health Products Regulatory Agency , December 30, 2020.
Ireland is expected to receive 3.3 million doses of the vaccine as part of the EU’s supply agreement. However, the EMA said it needed more information to rigorously assess the quality, safety and efficacy of this vaccine.
Other Covid-19 vaccines from Johnson & Johnson, CureVac, and Novavax are expected to release Phase 3 clinical trial data in the coming months. The EU has advance purchase agreements that would see Ireland allocate 2.2 million and 2.45 million doses of J&J and CureVac vaccines, respectively.
The Novavax vaccine, which is based on a more proven and tested technology of a viral subunit (protein) with an immune enhancer (adjuvant), generated very high levels of antibodies neutralizing the virus and protected against infection as well as disease in preclinical studies. However, the EU has not yet reached an agreement on the supply of this vaccine.
One approach to conserving vaccine stocks, championed by the UK, is to delay the administration of the second dose of vaccine, and thus to vaccinate more people with a single dose.
This approach has some advantages, especially for the younger population, but not for those at high risk or the elderly.
Immune responses tend to be stronger with a longer interval between primary and secondary vaccination. However, there is limited data from different clinical trials suggesting that one dose of a Covid-19 vaccine confers high levels of protection. Immune responses generally decline rapidly after a single immunization with non-replicating vaccines.
Another approach is to prioritize the vaccination of those who have not been infected with SARS-CoV-2, at least in the short term when the vaccine supply is limited. People who have recovered from an infection may not need to be vaccinated because they have already generated a protective immune response against the virus.
A study of healthcare workers in Oxford, published last week in the New England Journal of Medicine, showed that only two of 223 workers who had ever confirmed a SARS-CoV-2 infection were re-infected and both were asymptomatic, whereas there were 223. infections among 11,364 workers who had not previously been infected with SARS-CoV-2.
There have been nearly 128,000 PCR-confirmed cases of Covid-19 in Ireland. Based on current trends, we could have 300,000 cases in six weeks
This study suggests that natural infection confers 100% protection against Covid-19 disease and also gives very good protection against infection with SARS-CoV-2.
There are other documented cases of individuals re-infected with SARS-CoV-2, but this is 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 in six weeks. Vaccine stocks could be maintained by excluding these previously infected individuals from the initial vaccination program.
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% of all SARS-CoV-2 infections. While mass population serologic testing is logistically challenging, it would identify individuals who had asymptomatic infections, most of whom are known to develop antibodies. Although less clear than the confirmed PCR positive cases, this could allow the exclusion of another cohort from subsequent rounds of vaccination.
It could be argued that we do not know whether the antibodies prevent reinfection with SARS-CoV-2 or whether they persist for long periods after infection. However, scientific evidence from the recent New England Journal of Medicine report and studies of other pathogens suggest that antibodies protect against viral infections and can persist for months or years.
If the antibody levels drop to low levels, immune cells, called memory T and B cells, should persist and provide longer protection. Therefore, natural immunity must be exploited against an uncontrollable virus; at least until vaccine supply is no longer a problem.
Kingston Mills is Professor of Experimental Immunology and Academic Director of the Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland
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