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16th August 2021
Vaccines against COVID-19 have been administered across the globe and have been shown to be efficacious at preventing COVID-19 illness. However, with the emergence of viral variants, some of which are able to escape neutralising antibodies, there is an increased risk of vaccine breakthrough infections. While it is possible to modify existing vaccines to ensure that they are effective against variants of concern, an alternative strategy is to provide individuals with a third, or booster vaccination dose. In fact, there is animal data to suggest that a booster dose increases antibody titres to at least one variant of concern although whether this strategy will be effective in humans remains uncertain. One way of studying the value of a booster dose, is to compare the antibody response generated after full vaccination among those with and without prior infection. This was the objective of a study by a team from the Wolfson Centre for Global Virus Research, University of Nottingham, UK. They used data from the PANTHER Study which is designed to track frontline healthcare workers. For the present study, the researchers were interested in any differences in the antibody response among fully vaccinated individuals, in those with or without a prior COVID-19 infection. Participants were split into two groups (prior or no prior infection) and blood samples taken for analysis of IgG antibody levels to the wild-type COVID-19 and against two variants of concern, B.1.351 and P1 after both their first and second doses of vaccine which were given 10 weeks apart.
The total cohort consisted of 45 individuals with a mean age of 47.5 years (80% female) and 20 with a prior infection, all of whom had received two doses of BNT162b. The level of antibodies among individuals with a prior infection were higher after a single vaccine dose compared to previously uninfected participants. Interestingly, after the second vaccine dose, there was a significantly increased antibody response, not just to the wild-type COVID-19, but to the two variants of concern among those who had a prior infection compared with uninfected individuals.
Commenting on these findings, the authors suggested that their data showed how repeated exposure to COVID-19, i.e., through a prior infection and two doses of a vaccine, increased the level of neutralising antibodies. In other words, a prior infection much like a booster dose. Furthermore, it was also apparent that this increased antigenic exposure appeared to broaden an individual’s antibody response by creating neutralising antibodies to the two variants of concern. If confirmed in future studies, these results would be of enormous importance. For instance, if repeated exposure not only enhanced but extended immunity against variants of concern, there is a very strong argument for giving individuals a further, third, booster vaccine dose, even if this is directed at the original spike protein, to combat any new variants likely to emerge in the future.
Urbanowicz RA et al. Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection. Sci Transl Med 2021
5th August 2021
There is now clear evidence that vaccination against COVID-19 reduces symptom burden and duration of any associated illness. An emerging problem is the appearance of new COVID-19 variants, in particular, the COVID delta variant. However, an analysis by Public Health England, has shown that two doses of a COVID-19 vaccine, reduces the incidence of hospitalisation in those infected with the delta variant. Furthermore, in the US, the Centers for Disease Control and Prevention (CDC) produced updated advice indicating how a body of evidence now suggests that full vaccinated individuals were less likely to either acquire COVID-19 or transmit the virus onto others. However, despite this, there are emerging concerns, particularly from Israel, which has managed to vaccinate a large proportion of the adult population, that the reported effectiveness of COVID-19 vaccines has reduced to 64% with regard to preventing infection and symptomatic illness. Interestingly, this reduced effectiveness appears to coincide with the spread of the COVID delta variant in the country. This is of particular concern given how it is thought that the COVID delta variant has an estimated 60% higher risk of household transmission. Thus, some uncertainty remains over the effectiveness of vaccines against the COVID delta variant and the extent to which the risk of transmission is reduced.
Potential for increased transmission
In light of this uncertainty, the CDC has released data captured from an outbreak of COVID-19 during July 2021, associated with large, public gatherings, in Massachusetts. During the month of July, 469 cases of COVID-19 associated with multiple summer events and public gatherings were reported. The reported vaccination coverage among eligible Massachusetts residents was 69% although the majority (74%) of symptomatic infected cases occurred in fully vaccinated individuals, who had received either the Pfizer-BioNTech or Jansen vaccine. Most infections (85%) occurred in males with a median age of 40 years.
A total of 133 patients provided samples for genomic analysis, of which, 89% were due to the COVID delta variant. Fortunately, only five people required hospitalisation (four who were fully vaccinated) and no deaths were reported. PCR cycle threshold (CT) values, which represent a measure of the concentration of viral load present in a sample, were taken from 127 vaccinated and 84 unvaccinated individuals. The lower the CT value, the more viral material present and the median CT values were 22.77 and 21.54 for the vaccinated and unvaccinated individuals respectively. In order words, given that the transmissibility of COVID-19 is known to be dependent on viral load, it would appear that the infection with the COVID delta variant, even among fully vaccinated individuals, could still lead to appreciable transmission of the virus. As a result of these findings, the CDC has now suggested that prevention strategies such as mask wearing should continue indoors, irrespective of vaccination status.
7th June 2021
As mutations enable the emergence of COVID-19 variants, it is crucial to determine if the available vaccines are able to induce a satisfactory level of neutralising antibodies (NAbs) against any new variants. In a laboratory study, a team from the Francis Crick Institute and the National Institute for Health Research, set out to assess the level of NAbs produced in response to five COVID-19 variants, including the original viral strain as well as three others that have been deemed variants of concerns; B.1.167.2 (Delta or Indian variant), B.1.351 (South African variant) and the B.1.1.7 (UK variant). They also compared the level of NAbs produced in participants who had received either one or two doses of the BNT162b vaccine.
Among 159 participants who had received both doses of the vaccine, all samples produced a satisfactory NAbs response against each of the strains although six and nine individuals lacked detectable antibodies against the B.1.617.2 and B.1.351 respectively. However, despite the induction of NABs, levels were 5.8-fold less against the Delta variant compared with the original strain and 2.6-fold less against the B.1.1.7 although of a similar order of magnitude for the B.1.351. Interestingly, there was a significant correlation between NAbs and age, with titres significantly reduced among older individuals. A further finding of concern was that among a smaller cohort (14), who had been vaccinated between 8 and 16 weeks earlier, there was a significant reduction in NAbs titre against all of the variants.
Perhaps of most interest were the data from participants who had received only a single vaccine dose. After a median of 30 days post-vaccination, 79% of individuals had sufficient NAbs against the original strain, but this reduced to 50% for B.1.1.1, 32% for B.1.617.2 and to 25% for B.1.351.
In a discussion of these findings, the authors suggested that although NAbs levels are considerably reduced against the B.1.617.2 and B.1.351 after a single vaccination, this emphasised the importance of reducing the delay period (which has been set at 12 weeks) between doses.
Lead author of the study Emma Wall, said “This virus is likely to be around for some time to come, so we need to remain agile and vigilant. Our study is designed to be responsive to shifts in the pandemic so that we can quickly provide evidence on changing risk and protection”.
Wall EC et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet 2021