By Associate Professor James Ussher for Newsroom
It was evident early in the pandemic that vaccines would be necessary to avoid a huge death toll across the world.
Despite the rapid rollout of effective vaccines, vaccine inequity is still a massive issue and new variants continue to emerge in severely under-vaccinated countries. Ensuring equitable distribution must be a global priority.
How were vaccines developed so quickly?
The speed of development of COVID-19 vaccines is a true success story for biomedical science, built on many decades of research.
Firstly, next generation sequencing technologies allowed rapid identification of SARS-CoV-2 as the cause of the outbreak in Wuhan, China, and rapid public sharing of sequence data allowed vaccine developers to design their vaccines within weeks of the virus emerging.
Secondly, due to previous outbreaks of coronaviruses closely related to SARS-CoV-2 (SARS-CoV, and MERS-CoV), there had already been a substantial amount of research into coronavirus vaccines. Several had made it through to clinical trials where they had been shown to be safe and stimulate an appropriate immune response.
Thirdly, over several decades there had been much research into vaccine platform technologies, such as mRNA and viral vectors, that are rapidly adaptable to novel pathogens and whose manufacture can be rapidly scaled up for clinical use. These vaccine platforms were able to be quickly developed against SARS-CoV-2 by inserting the sequence of the antigen of interest (the spike protein).
Fourthly, due to the urgent global need for a vaccine, funding was not a limiting factor, so vaccine development could occur at the fastest possible pace.
Finally, clinical trials were conducted in an efficient manner by overlapping the different stages; all the essential phases of preclinical and clinical testing were completed. This allowed for much faster and more efficient assessment of the safety and efficacy of vaccines.
Safety and efficacy of vaccines
To date, nine SARS-CoV-2 vaccines have been approved for use and 16 authorised for emergency use in one or more countries; a further 109 are in clinical trials. Of those with approval for use in New Zealand or similar regulatory environments (United States, Canada, UK, EU, and Australia), two are mRNA vaccines (Pfizer's BNTB16b2 and Moderna's mRNA1273) and two are viral vectors (AstraZeneca's ChAdOx1 and Jansen's Ad26.S). Globally, approximately 8 billion doses of SARS-CoV-2 vaccines have been administered.
The Pfizer BioNTech vaccine is the main vaccine being used in New Zealand's COVID-19 vaccination programme. It has full approval from the United States's Food and Drug Administration for use in those 16 years and older and emergency use authorisation for five to 15-year-olds. In New Zealand, it has provisional approval from Medsafe for use in those 12 years and older.
There were more than 43,000 participants in the pivotal phase 3 efficacy trial, which demonstrated an efficacy against symptomatic SARS-CoV-2 infection of 95 percent. No major safety concerns were identified. Subsequent real world studies confirmed the effectiveness of the vaccine.
Intensive post-rollout monitoring identified anaphylaxis (an acute allergic reaction) and myocarditis as rare side effects of the vaccine. Anaphylaxis occurs at a rate of 4.7 cases per million doses and can be managed at all vaccination sites.
Myocarditis occurs in 2.7 per 100,000 people vaccinated, with higher rates observed in young males with the second dose. Importantly, the risk of myocarditis with COVID-19 is four times higher than with vaccination, is higher in all demographic groups, and follows a more severe course than vaccine associated myocarditis, which in the vast majority of cases is mild and rapidly resolves.
A cohort study of 6.4 million vaccinees and 4.6 million unvaccinated persons in the United States found no increase in mortality in vaccinees from non-COVID-19 related causes.
SARS-CoV-2 vaccines are highly effective at preventing COVID-19, hospitalisation, and death. To mid-September, Public Health England estimates that vaccination has prevented almost 24 million cases and over 123,000 deaths in England. In those aged 45 and over, more than 230,000 hospitalisations have been prevented.
Booster vaccination
Several recent studies have demonstrated waning of antibody levels and vaccine effectiveness against infection months after the primary course of vaccination. Despite this, protection against severe disease and hospitalisation remains high.
A booster dose has been shown to increase neutralising antibody levels 5.5 to 7.8 times one month after the booster dose compared with one month after the second dose. Furthermore, increased breadth of neutralisation against Beta and Delta variants is seen.
Several countries have now rolled out booster doses. Early data out of Israel suggest a large increase in protection against both infection and severe disease compared with those who have been vaccinated but not received a booster. The duration of this protection is not yet known.
Omicron and vaccine equity
The B.1.1.529. variant, first reported by South Africa on November 24, 2021, was declared a variant of concern on November 26, and given the name Omicron. It has more than 30 mutations related to the spike protein, including several that are predicted to confer partial escape from neutralising antibodies or to enhance transmission.
Further information is awaited about the current global distribution of Omicron, its transmissibility, the severity of disease that it causes, its ability to be neutralised by convalescent and post-vaccination sera, and the effectiveness of past infection or vaccination at protecting against infection and severe disease.
The emergence of Omicron highlights the lack of global vaccine equity and the risk that this poses to the world. The vast majority of Africa remains unvaccinated, with only 17 doses of vaccine administered per 100 people. Of the 37 countries with vaccine coverage of less than 20 doses per 100 people, 33 are in Africa. Non-African countries are Papua New Guinea, Afghanistan, Syria, and Haiti.
Such low vaccination coverage not only results in unnecessary morbidity and mortality, but also allows greater opportunity for viral variants to emerge. It should now be a global priority for effective vaccines to be provided to all countries and that as many eligible citizens as possible are vaccinated. COVAX is an existing mechanism for global vaccine supply and should be urgently funded by governments.
Associate Professor James Ussher is Science Director of the Vaccine Alliance Aotearoa New Zealand/Ohu Kaupare Huaketo and is on the Government's COVID-19 Vaccine Technical Advisory Group.
This article first appeared on Newsroom.co.nz.
