brand logo

Are the Covid-19 vaccines effective against Omicron? 

27 Dec 2021

BY Suranjith L. Seneviratne, Buddhika Samaraweera, Chamara Dalugama, Jayani Kariyawasam and Visula Abeysuriya  On 26 November 2021, the World Health Organisation (WHO) designated Omicron as a variant of concern. The high number of mutations noted in this variant, had the potential to make it more transmissible and/or resistant to the current vaccines and/or treatment. The variant has now spread to over 100 countries globally and extensive and rapid community transmission is taking place in many countries. It is more transmissible than the Delta variant. In the UK, Omicron infections are doubling every two or three days and it has become the dominant SARS-CoV-2 variant. Currently, amongst vaccinated populations, there is no evidence for an increased risk of severe disease or death due to the Omicron variant. However higher case numbers would still place a considerable burden on healthcare systems. The Covid-19 vaccination is known to induce neutralising antibodies and T-cells. Data has been released on vaccine effectiveness against the Omicron variant and this article would discuss the currently available information.  The Durban study  A small study from Durban, South Africa, tested the ability of serum obtained from individuals who received two doses of the Pfizer Covid-19 vaccine, to neutralise the Omicron variant. The result was compared with that obtained using the ancestral D614G virus. Plasma samples from 12 individuals were studied and a live virus neutralisation assay was used. Six individuals had a previous SARS-CoV-2 infection during the first wave in South Africa (where the infection was with the ancestral D614G virus), while the other six had not had a previous SARS-CoV-2 infection. A 41 fold decline in geometric mean titer (GMT) was seen with the Omicron variant compared to the D614G virus. The neutralising antibody escape was incomplete, with some previously infected persons showing relatively high neutralisation titres with Omicron. Booster vaccine doses were not specifically tested in this study. Those who were vaccinated after an earlier episode of Covid-19 had more protection. It is known that two vaccine doses given after a prior SARS-CoV-2 infection produces a large increase in antibody levels.  The Pfizer study This study tested a panel of serum samples from individuals that received two or three 30-μg doses of the Pfizer Covid-19 vaccine. The sera were collected, three or four weeks after the individuals received the second or third dose of the Pfizer vaccine respectively. A pseudovirus neutralisation test was used and each serum sample was tested for its neutralising antibody titre against the wild-type SARS-Cov-2 spike protein and the Omicron spike variant. The third dose increased the neutralising antibody titres against the Omicron spike by 25-fold. After three doses of the Pfizer vaccine, neutralisation against the Omicron variant was comparable to the neutralisation against the wild-type strain in individuals who received two doses of the Pfizer vaccine. Sera from individuals who received two doses of the Pfizer Covid-19 vaccine showed on average, more than a 25-fold reduction in neutralisation titres against the Omicron variant compared to the wild-type. This indicates that two doses of the Pfizer vaccine may not be sufficient to protect against infection with the Omicron variant. The geometric mean titre (GMT) of neutralising antibodies against the Omicron variant was 154 (after three doses). It was 398 against the Delta variant (after three doses) and 155 against the ancestral strain (after two doses). Thus a third dose provides a similar level of neutralising antibodies to Omicron as is observed after two doses against wild-type and other variants that emerged before Omicron. After a booster dose of the Pfizer vaccine, the persistence of neutralising antibody titres over time against the Omicron variant is still unknown. Two doses of the Pfizer vaccine may still induce protection against severe disease, as 80% of epitopes in the spike protein that are recognized by CD8+ T cells are not affected by the mutations in the Omicron variant. A booster dose strongly increases CD8 T cell levels against multiple spike protein epitopes that are considered to correlate with the protection against severe disease.  The Moderna study On 20 December, it was reported that two doses of the Moderna vaccine produced low levels of neutralising antibodies against the Omicron variant. In this study, serum from Moderna-vaccinated individuals was tested against a pseudovirus that mimicked the Omicron variant. Whether the two doses would reduce hospitalisations or deaths from the Omicron variant was not mentioned. A 50-microgram booster dose increased neutralising antibody levels against the Omicron variant by 37-fold. In addition, a 100-microgram booster (which is the dose found in the first and second vaccine doses) increased neutralising antibody levels to more than 80 times pre-boost levels. Currently, it is the 50-microgram dose that is approved as the Moderna vaccine booster dose. The 100-microgram dose is generally safe and well tolerated, but has marginally more frequent adverse reactions. The UK Health Security Agency (UKHSA) study A recent report by the UKHSA stated that two doses of a Covid-19 vaccine were significantly less effective at preventing symptomatic disease by the Omicron variant compared to Delta. The final analysis was on 56,439 Delta and 581 Omicron cases. Booster doses of the Pfizer vaccine were found to provide a significant increase in protection against mild disease and are likely to offer even greater levels of protection against severe disease. People who had two doses of the AstraZeneca vaccine, 25 or more weeks earlier, had lower protection against symptomatic infection with Omicron (10%) than Delta (40%). A similar trend was seen in those who have had two doses of the Pfizer vaccine. There is around 60% protection against Delta at 25 or more weeks after the second dose and just under 40% with Omicron. If a Pfizer vaccine booster is given after two AstraZeneca or Pfizer vaccines, the level of protection is increased. From two weeks after a Pfizer booster dose, vaccine effectiveness increased to around 71% among those who received AstraZeneca as the primary course and around 76% among those who received Pfizer as the primary course. The study was not able to determine protection against severe forms of disease. This aspect is important as a drop in effectiveness against severe infections from 96% to 92% could lead to double the number of people that are not protected against hospitalisation. With previous variants, vaccine effectiveness against severe disease, including hospitalisation and death, has been higher than effectiveness against mild disease. It will be a few weeks before effectiveness against severe disease with Omicron can be estimated. However based on this experience, this is likely to be substantially higher than the estimates against symptomatic disease. After the emergence of the Delta variant in the UK, early estimates of vaccine effectiveness against mild infection following two doses of a Covid-19 vaccine were substantially attenuated in comparison to Alpha. However, analysis of protection against hospitalisation showed no diminution of protection when comparing the Delta and Alpha variants.  The Oxford University study In this study, blood samples obtained from people 28 days after a second dose of either the Oxford-AstraZeneca or Pfizer vaccine were tested. When Omicron was introduced to those samples, a substantial fall in neutralising antibodies was observed when compared to the immune responses against earlier variants. It was concluded that two doses of the Oxford-AstraZeneca or Pfizer Covid-19 vaccines are substantially less effective at warding off Omicron compared to previous SARS-CoV-2 variants. Some vaccine recipients failed to neutralise the virus at all.  Discovery Health study  This study was done by Discovery Health (South Africa’s biggest medical-insurance provider) and the South African Medical Research Council. It was based on more than 211,000 Covid-19 test results in South Africa from 15 November to 7 December 2021, with around 78,000 positive results attributed to Omicron. Two doses of the Pfizer vaccine may offer 70% protection against being hospitalised with the Omicron variant. Thus it appears that two doses of the Pfizer vaccine were less effective at keeping people infected with the Omicron variant out of hospital as the value was 93% during the previous Delta infection wave. The protection was maintained across age groups and in the face of a range of chronic illnesses including diabetes, hypertension, hypercholesterolemia and other cardiovascular diseases. In addition, two doses of the Pfizer vaccine were 33% effective against infection by the Omicron variant. The equivalent level for the Delta variant was 80%. These findings need to be considered preliminary, as cases attributed to Omicron were based on the relative prevalence of the variant within the country and all were not confirmed by sequencing.  The Boston study This study measured the levels of neutralisation against the wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses, of serum samples from 111 Pfizer, 88 Moderna and 40 Johnson & Johnson vaccine recipients. Those who were vaccinated recently (three months ago), distantly (six to 12 months ago), received a booster vaccine dose recently or who had prior a SARS-CoV-2 infection were studied. Neutralisation of the Omicron variant was undetectable in most vaccinated individuals. However, individuals boosted with the Pfizer or Moderna vaccines exhibited potent neutralisation of Omicron only 4-6-fold lower than wild type. This suggested that mRNA Covid-19 vaccine boosters increased the cross-reactivity of neutralising antibody responses. The study highlights the importance of boosters to broaden neutralising antibody responses against highly divergent SARS-CoV-2 variants.  The Hong Kong study This study found two doses of either the Pfizer or Sinovac vaccines did not produce sufficient levels of antibodies against the Omicron variant. In a group of 25 double vaccinated Sinovac (Coronavac) vaccine recipients, the serum of all the individuals did not contain sufficient levels of antibodies to neutralise the Omicron variant. This has important global implications as currently, Coronavac, is the world’s most widely-used Covid-19 vaccine, with almost two billion doses distributed globally to countries such as Indonesia, Brazil, the Philippines, Turkey, Albania and Ukraine. Among a group of 25 double-vaccinated Pfizer recipients, five individuals had sufficient levels of neutralising antibodies, reducing the vaccine’s efficacy to 20-24%. Imperial College London studies These studies found that Omicron largely evades immunity from past coronavirus infection or two vaccine doses, and that boosters are key to mitigating the impact of the Omicron variant. All PCR-confirmed Covid-19 cases in England from samples taken between 29 November and 11 December 2021 were analysed. The risk of reinfection with Omicron was 5.4 times higher than with Delta. The protection from a past infection, against reinfection by Omicron was as low as 19%. The level of antibodies produced against Omicron was estimated to be 4.5-fold lower than against Delta. During the period of the study, the proportion of Omicron was doubling every two days and the reproduction number for Omicron was above three. There was no evidence of Omicron having a lower severity of disease than Delta. Data on hospital admission was very low at the time of this study. For those who were two or more weeks past their second vaccine dose, and two or more weeks past their booster dose (for both Pfizer and AstraZeneca vaccines), there was a significantly increased risk of developing a symptomatic disease with Omicron when compared with Delta. Vaccine effectiveness estimates against symptomatic Omicron infection was between 0% and 20% after two doses, and between 55% and 80% after a booster dose. After a booster vaccine with Pfizer or Moderna, neutralising antibodies were estimated to increase by 1.6 and 3.3-fold compared with levels after dose two of the Pfizer or Oxford-AstraZeneca vaccine respectively. This reduction in neutralising antibodies may affect vaccine efficacy against severe disease. If the antibody decay rate after a booster dose is the same as that observed after the first two doses, by 60 days after the primary vaccine course followed by a Pfizer booster dose, it was predicted that vaccine efficacy against severe disease may drop from 96.5% against Delta to 80.1% against Omicron. If the rate of decay was half that rate, the corresponding values were 97.6% against Delta to 85.9% against Omicron.  Columbia University study  This study found the Omicron variant to be markedly resistant to neutralisation by serum from convalescent patients and individuals vaccinated with one of four widely used Covid-19 vaccines (that is the Pfizer, Moderna, Oxford-AstraZeneca and Johnson & Johnson vaccines). Even those who were boosted with the mRNA-based vaccines showed diminished neutralising activity against Omicron. The study also evaluated a panel of monoclonal antibodies and found the activity of 18 of the 19 antibodies that were tested, to be either abolished or impaired. The spike mutations S371L, N440K, G446S and Q493R conferred greater antibody resistance to Omicron.  Omicron infection after a booster dose A report of Omicron variant cases in a group of people who had also received their booster doses has been released. Here a group of seven German tourists (in their twenties and thirties) who visited South Africa recently, were subsequently found to have been infected with the Omicron variant. All had mild to moderate symptoms and were not admitted to hospital. This report raises the possibility that even three Covid-19 vaccine doses may not always protect against symptomatic illness in some individuals. If this pattern becomes more prominent in the future, then the role of Omicron-specific vaccines may take on a more important role.  Omicron-specific vaccines Vaccine makers are already modifying their vaccines to create Omicron-specific vaccines in case these were needed in the future. On 25 November 2021, Pfizer stated they have commenced developing an Omicron-specific version of their vaccine and that following regulatory approval the first batches should be ready for delivery within 100 days. They have predicted their vaccine candidate could be ready for regulators to consider by March 2022. Moderna is also working on an updated version against the Omicron variant. Both Johnson and Johnson and AstraZeneca are also progressing on this front.  Vaccine access inequity  Inequity of vaccine access has contributed to a large extent to the continued uncontrolled transmission of the SARS-CoV-2 virus. This in turn, would increase the chances of emergence of new viral variants, some of which would turn out to be clinically significant. In recent months, there has been much debate on the use of booster vaccine doses in some countries. Some have forcefully argued that the best way to stop the continued spread of the SARS-CoV-2 virus, is to make sure that lower income countries have good access to the Covid-19 vaccines. Two vaccine doses have been administered to only 1.9% and 38.4% of eligible individuals in Nigeria and India, whilst the percentage in the UK and Sri Lanka is 69.7% and 62.9% respectively. As at 12 December 2021, 4.7% individuals in the world have received a booster vaccine dose, with widely varying rates in different countries (UK – 36.8%, US – 17%, Israel – 44.9%, Sri Lanka – 7.5% and none in Nigeria and India). It has been argued that the pandemic would not be controlled by the administration of multiple booster vaccine doses to all persons in high income countries.  Conclusions  The Omicron variant is poised to become the predominant SARS-VoV-2 variant globally. The rapid roll out of vaccines to areas of the world that are lagging in this respect is very important. The use of booster doses show improved neutralisation against the Omicron variant. Laboratory data suggests, the more neutralising antibodies a person has, the better the clinical outcome may be. The overall advice should be for persons to get vaccinated and to receive the booster dose, even if they have been infected previously.


More News..