Omicron shows the urgent need for a catch-all vaccine

Within two months of November 2021, when the SARS-CoV-2 Omicron variant was first reported by South Africa, Omicron replaced the Delta wave in countries facing a surge.

As scientists raced to investigate Omicron’s capacity to spread and cause disease and its susceptibility to vaccines and booster doses, they soon found it spread very rapidly and infected vaccinated people quite well. They also knew that it may be blocked reasonably effectively by administering booster doses and that it caused mostly mild illness compared to the Delta variant. Some experts say this may represent a trade-off between transmissibility and lethality of the virus as it evolves.

In South Africa, where the Omicron variant represented less than 1% of samples tested on 1 November 2021 its share exceeded 99% by 17 January 2022. In the UK, the US and Denmark, by January 18, Omicron accounted for 97%, 91% and 97%, respectively, of samples sequenced. In India, the share of Omicron was 94% by January 24.

Using preliminary data the R-value for the Omicron variant was estimated at 2.4 in the Gauteng province of South Africa and about 3.5 in England. In contrast, the R-values in South Africa and England were below 1 late October and in early days of November, when Delta was the dominant variant accounting for >95% of COVID-19 infections tested.

Why Omicron spread so efficiently?

Scientists at the University of Hong Kong cultured pieces of bronchus from patients getting treated for respiratory illness and exposed them to different SARS-CoV-2 viruses: the parental 2020 virus, the Delta and the Omicron variants, separately. They reported in December 2021 that the Omicron variant multiplied to very high levels compared to the Delta variant, and the parental virus within 24 hours.

Other experiments suggested that Omicron has a heightened ability to get past the immune system.

Omicron evades immunity acquired by natural infection

Scientists in South Africa examined COVID-19 national surveillance data and identified people who tested positive for SARS-CoV-2 infection until the end of August 2021, three months prior to Omicron’s emergence. They premised their work on the assumption that if by end November 2021, any of these people tested positive again for SARS-CoV-2 infection, they are likely to be cases of re-infections by Omicron.

In their pre-print on December 2, 2021, scientists concluded that reinfections increased in South Africa in line with the spread of Omicron. Soon, the Centers for Disease Control and Prevention (CDC) also documented that Omicron is capable of infecting individuals infected by SARS-CoV-2 in the past.

Omicron also evades vaccine-induced immunity

In its Morbidity and Mortality Weekly Report of December 17, the CDC documented 43 Omicron patients of whom 25 were fully vaccinated, nine had received a booster dose at least a fortnight prior to the onset of COVID-19 symptoms.

How does Omicron evade prior immunity?

Immunity against infections is mediated by Y-shaped protein molecules called antibodies — infection-fighting proteins produced after infection or vaccination. People infected by SARS-CoV-2 or vaccinated (most vaccines are designed to elicit antibodies to the spike protein of the parent SARS-CoV-2) will have antibodies uniquely specific to the spike protein of SARS-CoV-2.

Spike antibodies can attach tightly to that part of the spike protein key for SARS-CoV-2 to attach to cells thus blocking virus entry and preventing infection. Infection-blocking antibodies are known as neutralising antibodies.

Scientists observed that (i) the spike protein of the Omicron variant is very different from the parental virus and the preceding variants, and (ii) the Omicron variant infects people with prior immunity whether acquired by natural infection or vaccination.

All current COVID-19 vaccines are designed to elicit antibodies to the parental SARS-CoV-2 spike protein. The Omicron spike protein, with about 30 odd mutations, is sufficiently different to be missed by the vaccine-induced antibodies.

This raises questions about the level of protection that COVID-19 vaccination affords against Omicron infection?

How effective are vaccines against Omicron?

In the two months since Omicron was identified, several studies such as the UK Health Security Agency (UKHSA) reported that AstraZeneca vaccine was not effective at preventing symptomatic Omicron illness at around four months after the second dose. Two doses of the Pfizer vaccine, which offered high protection (about 88%) against symptomatic Omicron and Delta illness up to two months after the second dose, waned to quite low levels (about 48% and 35% against symptomatic illness by Delta and Omicron, respectively) by the third month.

Two weeks after a booster dose of the Pfizer mRNA vaccine, effectiveness against symptomatic Omicron illness rose to 71% in those who had received two doses of the AstraZeneca vaccine, and to about 75% in those who had received two doses of the Pfizer vaccine. Beyond two weeks, this level of protection showed a decline.

Booster doses confer a good measure of protection against Omicron infection, as shown in some studies. This has been shown by demonstrating (i) increases in Omicron-neutralizing antibody titres in the blood of volunteers who received booster shots and (ii) reduction in the risk of developing symptomatic COVID-19 in Omicron patients who had received booster shots.

But protection offered by a booster dose is transient and will wane with time.

The Indian government on 22 January 22 announced the COVID-19 pandemic was in the community transmission phase. Indian modelling experts had predicted the third wave was underway since mid-December of 2021 and will peak by February 2022.

Boosters have limited impact

India announced a third dose of the same vaccine people received earlier, calling it ‘precaution doses’, for vulnerable sections of the population. A third dose of the inactivated COVID-19 vaccine Covaxin may boost immunity in those who have received two earlier shots of the same vaccine.

But this may not hold true for a third dose of the adenovirus-based Covishield vaccine, because of the recognized capacity of adenoviruses to stimulate high levels of adenovirus-specific antibodies. Titres of antibodies to the adenoviral component of Covishield in twice-vaccinated recipients could be so high as to render a third dose without any significant benefit. This aspect has not been investigated by scientists.

Omicron’s arrival in the pandemic landscape is akin to a game of snakes and ladders. Because booster immunity can wane, many tout additional boosters as the answer. The founder of the company BioNTech, which co-developed the mRNA vaccine with Pfizer, believes people should take not just a third dose but a fourth dose as well to stay protected. While he cites scientific evidence to show that booster shots are working, his advocacy of a fourth shot is tacit acknowledgement that the booster effect will wane.

Vaccine makers are talking of updating their vaccines to match new variants as they emerge. New variants are bound to emerge if Omicron is allowed to spread.

Omicron has shown the need for an effective transmission-blocking vaccine that will protect from both infection and disease. Rather than race to make new variant-specific vaccines, which would offer only temporary protection, vaccine makers, should invest in quickly designing and developing variant-proof vaccines.

The kind of scientific and technological prowess and collaboration that has come to the fore during the pandemic argue for the feasibility and success of such an initiative.

Sathyamangalam Swaminathan is a virologist formerly with the International Centre for Genetic Engineering and Biotechnology, Delhi.