The rapid and inexorable spread of the coronavirus disease 2019 (COVID-19) pandemic led to the intensive research effort to bring out safe and effective vaccines against the causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This culminated in the rollout of several vaccines built on nucleic acid, inactivated whole virus, and viral vector platforms, all with high efficacy against the ancestral variant of the virus.
However, the emergence of many newer variants with differing degrees of immune escape capabilities, coupled with significant vaccine hesitancy, challenged most national and international health authorities and governments’ goal to end the pandemic. A new study reports recent findings of the effectiveness of these vaccines against the Omicron (B.1.1.529) variant of SARS-CoV-2.
Introduction
Despite the deployment of two, three, or even more doses of highly effective vaccines such as the messenger ribonucleic acid (mRNA) vaccines from Pfizer and Moderna, there has been a surge in COVID-19 cases in many different countries. This led to questions about the real-world effectiveness of the vaccines in the face of increasingly prevalent immune escape variants like Omicron. This variant has the highest number of mutations reported so far among all variants, including many in the dominant spike antigen, in the receptor-binding domain (RBD).
Omicron cases first showed an uptick in late November in the UK, where more than 60% of those aged 20 years or more are vaccinated with two doses of either BNT162b2 (Comirnaty, Pfizer–BioNTech), ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca), or mRNA-1273 (Spikevax, Moderna) vaccines. Among those aged 50 years or more, over 80% had received two doses.
The booster doses were initiated at six months from the primary course, but this was later reduced to three months when faced with the Omicron variant’s rapid spread.
In the current study, reported in The New England Journal of Medicine, the researchers aimed to estimate how effective vaccination was against severe COVID-19, caused by Omicron and Delta variants of the virus, in England. All participants had received a primary course of the mRNA vaccines BNT162b2 or mRNA-1273, or the viral vector vaccine ChAdOx1 nCoV-19, and a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273.
Vaccine effectiveness against symptomatic disease was calculated after 1) the primary course and 2) the booster dose.
What did the study show?
The study period extended between November 27, 2021, and January 12, 2022, with over 885,000 individuals who had Omicron infection, over 200,000 with Delta infection, and over 1.5 million individuals who tested negative for the virus.
The findings showed that the vaccines were much more effective against the Delta than the Omicron variants, independent of the time point of evaluation, or the exact combination of vaccines used.
Interestingly, the ChAdOx1 nCoV-19 vaccine did not show any protective effect against symptomatic disease with Omicron after two doses when assessed at five months from the second dose. Conversely, two BNT162b2 doses protected against symptomatic disease for a month or so, reducing the risk by 66% at 2-4 weeks but by less than 10% at six or more months.
In comparison, two doses of this vaccine protected against 83% of Delta symptomatic cases at 2-4 weeks and 44% after six months.
For those who had a primary course of the ChAdOx1 nCoV-19 vaccine, followed by a BNT162b2 booster, the immediate efficacy (within a month of the booster dose) was 62% against symptomatic disease with Omicron. The corresponding risk reduction was 70% with an mRNA-1273 booster at 2-4 weeks. At 10 weeks, however, the BNT162b2 and mRNA-1273 booster prevented 40% and 60% of symptomatic cases with Omicron, compared to similar cases among the unvaccinated.
Among those who had two doses of the BNT162b2 vaccine and a homologous third booster dose, the risk of symptomatic disease dropped by 67% at 2-4 weeks, while it cut the risk in half at 10 or more weeks. If the mRNA-1273 booster was used instead, the result was a drop in symptomatic cases by 74% at 2-4 weeks and 64% at 5-9 weeks.
Against Delta, a primary course of the mRNA vaccines was more protective than the ChAdOx1 nCoV-19 vaccine at all points. Irrespective of the primary course, an mRNA booster initially provided over 95% protection against Delta, which remained high for 10 or more weeks.
What are the implications?
The findings of this comprehensive vaccine study show that two doses with the ChAdOx1 nCoV-19 or BNT162b2 vaccine were not very useful in protecting against symptomatic COVID-19 caused by Omicron compared to the useful protective immunity induced against Delta symptomatic disease. A third dose of either mRNA vaccine improved short-term protection, but this immunity rapidly waned.
The far fewer hospitalizations caused by Omicron during the study period made it difficult to estimate the protection offered by the vaccines against severe and fatal COVID-19. With Delta, the vaccines offered durable protection against severe outcomes of COVID-19.
This study thus corroborates earlier research that indicates a drop in neutralizing activity by 20-40 times after a primary course of BNT162b2, when faced with Omicron as against the ancestral variants, and by 10 times at least when Omicron is compared with the Delta variant. This reduction is still higher after a primary course of ChAdOx1 nCoV-19 vaccination, with many serum samples showing undetectable neutralizing activity against Omicron before a booster dose was administered.
The poor response with a primary course of ChAdOx1 nCoV-19 vaccine must be interpreted while keeping in mind that this vaccine was administered earliest and thus has the longest gap between primary vaccination and exposure to the Omicron variant, with the correspondingly lowest level of immunity. Secondly, it was administered to the highest-risk groups, while the mRNA vaccines have been the major vaccines used in younger populations and were rolled out in England later in the pandemic.
Despite these apparently discouraging findings, the scientists insist that “on the basis of experience with other variants and early estimates of hospitalization rates, vaccine effectiveness against severe disease is likely to be substantially higher than the estimates against symptomatic disease.” Further research will be necessary to validate this assertion.
