Nine Months Later, 25 Takeaways From the World’s COVID-19 Vaccination Programme

These takeaways cover how vaccines offer protection, the various efficacies of different vaccines, how vaccine protection stacks up against 'natural protection' and more.

On December 8, 2020, the UK became the first country to administer a COVID-19 vaccine to a person outside a trial, ahead of its nationwide vaccination programme. In the nine months since, more than 5.41 billion vaccine doses have been administered worldwide. Here are 25 major takeaways from this important international programme.

1. COVID-19 vaccines are highly efficacious against severe disease, hospitalisation and deaths in fully vaccinated individuals. Study after study from different countries, on disparate continents, using different vaccines has confirmed this.

2. Vaccines have only a minimal impact on transmission. They are not able to halt or prevent the development of a new surge. The current crop of vaccines are also good at staving off symptomatic COVID-19 disease but fail to suppress an infection entirely; instead, they have been known to ‘turn’ symptomatic infections into asymptomatic ones.

3. Different COVID-19 vaccines have different effectiveness, particularly against the infections of the delta variant. The data thus far indicates that the Johnson & Johnson vaccine has an efficacy of approximately 67%; Moderna, 66-95%; and Pfizer/BioNTech, 42-96%.

4. Almost all COVID-19 vaccines are safe to use. Only a few serious types of health problems after vaccination have been found to date and all of them are rare. These are anaphylaxis (severe allergic reaction), vaccine induced thrombotic thrombocytopenia (VITT), and myocarditis/pericarditis in adolescents and young adults. The known and potential benefits of COVID-19 vaccines outweigh their known and potential risk. Serious side-effects that could cause long-term health problems are extremely unlikely.

5. There is a significant waning of vaccine effectiveness against infection and symptomatic disease. It is more pronounced with mRNA vaccines than with viral vector vaccines (including AstraZeneca/Covishield). The dynamics of the immune response following the second dose differs significantly between the two vaccine types, with Pfizer’s mRNA jab demonstrating higher initial efficacy against people whose infections are nascent. However, its protection declines faster when the viral burden is higher and if the infection is symptomatic. There seems to be no evidence that its efficacy has varied by the inter-dose gap.

6. Prior COVID-19 infection along with a dose of a potent COVID-19 vaccine offers the most robust protection, especially against the variants of concern (VoCs). A single dose of a COVID-19 vaccine is also sufficiently efficacious against the development of COVID-19 disease in previously infected individuals.

7. The potency of a vaccine-given protection may start to wane as early as two months after the second dose, with mRNA vaccines. A recent study in Israel suggested that breakthrough infections in recently vaccinated people could appear within two months after their second dose.

8. Vaccines may reduce the viral load in vaccinated individuals, although the strength of this reductive potential diminishes after six months.

9. We don’t yet know if vaccine-induced protection really wanes or if the vaccine is unable to counter the delta variant as effectively as older strains. The decline in effectiveness is not entirely surprising. Bothe the factors may be operational against the Delta variant. Waning effectiveness over time, combined with the more contagious delta variant and the end of masking mandates, have boosted cases of COVID-19 among fully vaccinated persons.

10. Most vaccines could do with booster doses, six months after the second dose, to continue to protect against infection and symptomatic disease. Israel has become the first country to roll these doses out.

11. A dose of an mRNA vaccine for COVID-19 may have a significant impact on the body’s production of neutralising antibodies (Moderna > Pfizer > CureVac). In a recent study, among previously uninfected people, those who were inoculated with the Moderna vaccine had 2.6x more antibodies than those who had received the Pfizer vaccine. Similarly, among those who had been previously infected with COVID-19, those who had received the Moderna shot showed more antibodies than those who had received the Pfizer shot.

12. Studies aren’t yet conclusive, but titres of neutralising antibodies appear to be the main correlate of protection to evaluate COVID-19 vaccines – and not T-cells (CD4 and CD8). They are highly predictive of immune protection from symptomatic disease. However, we still don’t know the cut-off levels, i.e. the minimum titre of neutralising antibodies a vaccine needs to induce to claim it ‘works’.

13. Neutralising antibodies are the mainstay of protection against infection. In the immune-response arsenal, antibodies offer best long-term hope against COVID-19. T-cells may not be required for vaccine-mediated protection or reinfection.

14. Two-dose vaccines may not provide durable immunity. We need three-dose vaccine schedules for most vaccines. Concerns over waning immunity and VoCs have convinced some countries to deploy additional doses, even if it still isn’t clear to experts whether most people need them. Israel, however, no longer considers people who have received two Pfizer vaccine doses to be fully vaccinated; they need three doses.

15. Boosters work. Researchers have found signs that the Pfizer mRNA vaccine booster can cut infection risk by 70% or more, in Israel. But we don’t yet know a booster’s duration of protection. It is possible we will need multiple boosters.

16. We still don’t know whether a ‘variant-specific’ booster will be more effective than a booster designed against the ‘original strain’ – in the midst of an outbreak propelled by a specific variant.  There is also no consensus whether a heterologous booster (i.e. using an mRNA booster for a viral-vector vaccine or vice versa) will yield results.

17. Booster doses of viral-vector vaccines are expected to be efficacious as intended. Some experts were wary of interference with pre-existing vector-induced immunity, but studies from the UK have since dispelled this fear.

18. A longer gap between two doses of mRNA and viral-vector vaccines improves immunogenicity and subsequent vaccine effectiveness. We already know that the AstraZeneca vaccine has been known to become more immunogenic with a greater inter-dose gap (up to a point); other studies suggest that a longer interval between two doses of mRNA vaccines could be similarly better.

19. Mixing-and-matching COVID-19 vaccines can trigger a potent immune response. Several studies with different vaccines have found that combining different vaccines in a single schedule could be beneficial – although experts still seek answers to questions about real-world efficacy and rare side-effects.

20. There has been no final word yet on whether all children will need to be vaccinated against COVID-19. Considering the very low risk of serious disease in those aged 12-15 years without an underlying health condition that puts them at increased risk.

21. Studies have now confirmed something many suspected throughout the pandemic: natural infection confers longer and stronger protection against infection, symptomatic disease and hospitalisation than vaccination. However, this does not mean natural infection is preferable in any sense to vaccination.

22. The advent of new VoCs, especially those with significant immune-escape potential, has rendered all strategies based on achieving ‘herd immunity’ redundant. On the flip side, herd immunity isn’t the only way for us to complete a transition to normalcy.

23. There has been no evidence of antibody-driven disease enhancement (ADE) with the current crop of COVID-19 vaccines so far. Hundreds of millions of people have been inoculated to produce antibodies against the non-delta protein domains, and who are now exposed to the delta variant. There have been no reports of ADE in this population.

24. ‘Vaccine equity’ has become a joke, thanks to vaccine nationalism, apartheid and other forms of discrimination. The world today is 28% fully vaccinated, which may sound impressive. But consider the breakdown: “While high-income countries are 54% fully vaccinated and upper-middle-income ones 46%, the poorer half of the world lags considerably. Lower-middle-income countries stand at merely 10% and low-income countries at 0.7%.”

25. Vaccines are not silver bullets. We need non-pharmacological interventions along with vaccines to take on the delta variant and other future VoCs.

Dr Vipin Vashishtha, MD, FIAP, is a consultant paediatrician at the Mangla Hospital and Research Centre, Bijnor.