Vaccine-related papers

Third dose effectiveness and safety

The CDC has released more data from Pfizer on the safety and effectiveness of a third dose of their vaccine. The trial compared 5,000 adults who received a third dose with 5,000 matched double vaccinated people who received a placebo about 10 months after the second vaccine dose. The relative vaccine efficacy of the third dose was 95.3% between one and eight weeks after the dose. There were no significant adverse effects from the third dose.

In another study, binding and neutralising antibody levels were significantly higher after a third dose of the Pfizer/BioNTech or Moderna vaccines. Neutralisation of the Delta variant was lower than for the wild-type virus after the third dose

Only 49 participants were in the study, and antibody responses were only assessed one or two weeks after the third dose. The paper has not yet been peer reviewed.

A fourth vaccine dose can help some transplant recipients

A fourth mRNA vaccine dose can modestly improve antibody levels in transplant patients. Levels at four weeks post-dose were improved substantially in patients who had produced antibodies after a third dose. For patients who had not generated antibodies after a third dose 42% did so after the fourth dose, though often at very low levels.

Neutralising antibody and T cell levels remained low after a fourth dose. So, transplant patients will require additional protections from infection. The study involved only 37 patients. The paper was published in JAMA Network Open.

Vaccinated prisoners still at high risk

A study in a US prison found that vaccinated inmates were as likely to become infected as unvaccinated inmates. Duration of infections and viral loads were also the same.

In the study less than 20% of participants were unvaccinated, which may affect the robustness of some of the findings. The effect of time since vaccination and infection status was not examined, so the extent to which the results may be due to waning effectiveness is unknown.

A prison is regarded as a very high risk setting for transmission, and is a very different environment from normal households or workplaces. So, the results are not generalisable, but do indicate that masks and other measures are required alongside vaccinations to control transmission in high risk environments. The paper has not yet been peer reviewed.

Improving vaccine effectiveness

Changes in the non-coding regions of the mRNA vaccine CureVac improves the immune response in macaques, compared with the first version of the vaccine. The changes improved expression of viral antigens, and increased both binding and neutralising antibody levels.

Animals vaccinated with the modified vaccine had lower viral loads than those who received the original. generated 10-fold higher neutralising antibody responses to several viral variants were over 10-fold higher with the modified vaccine.

The results may be applicable to the other vaccines using the spike protein. The paper was published in Nature.

Waning vaccine effectiveness against infection

A review of 14 vaccine effectiveness studies found that while effectiveness against severe disease in the six months after full vaccination declined by up to 10%, most remained above 70% effective. Effectiveness against infection declined on average by 18.5% between one and six months, and by 25.4% for symptomatic infections. Declines were greater in those over 60.

Four vaccines were included in the studies, but most involved Pfizer/BioNTech or Moderna. The paper has not yet been peer reviewed. ​​

Analysis of over 80,000 Israeli health records showed an increasing risk of infection after 90 days following the second Pfizer/BioNTech dose. Infection risk more than doubled after 90 days, compared with the risk in the first 90 days.

In the first 90 days 1.3% of those vaccinated became infected, with this increasing to 2.4% between 90 and 120 days, and 15.5% beyond 180 days.

The study did not assess the severity of Covid-19 at different time points following vaccination. The paper was published in The BMJ.

A Japanese study found that older people (60-70 years old) and smokers had lower antibody titres six months after vaccination than other groups. Between three and six months post-vaccination the antibody titres declined by around one third, with declines in women greater than that for men. The results are based on tests of 365 healthcare workers at a single hospital vaccinated with the Pfizer/BioNTech vaccine. The paper has not yet been peer reviewed.

Pfizer effectiveness and safety in 12-18 year olds

The Pfizer/BioNTech vaccine was found to be very effective in preventing severe Covid-19 in 12 to 18 year olds. Effectiveness in preventing hospitalisation was 93%. This was based on 179 hospitalised Covid-19 cases between July and September, of which only six were vaccinated.  It is too soon to determine if, or by how much, this level of protection persists. The paper was published in Morbidity and Mortality Weekly Report.

Correlates of protection for the Moderna vaccine

The neutralisation antibody titre (concentration) was found to correlate with the degree of protection provided by the Moderna vaccine. The degree of protection also correlated with the levels of a range of binding antibodies when measured at days 29 and 57 after full vaccination. The paper was published in Science.

Vaccination and long Covid

A news article in Nature discusses the evidence for the effects of vaccinations on long Covid. It is difficult to reach firm conclusions at this stage because people with no or very mild symptoms may not be tested, so prevalence estimates will not be accurate. Vaccinations are likely to have some effects, but the size and nature of them require further study. Since vaccinations reduce the risk of infection, and protect against severe disease, incidence of long Covid is expected to reduce.

A letter in Nature Medicine notes the nine major UK studies investigating long Covid.

Modest effectiveness of an inactivated virus vaccine

The inactivated SARS-CoV-2 virus vaccine BBV152 (Covaxin) was found to be 47% effective against symptomatic infection two weeks after the second dose. This is based on Indian healthcare workers who had no evidence of a prior infection. Effectiveness was 50% when cases with prior infections were included.

The results are lower than those found during an earlier clinical trial, and are attributed to the current dominance of the Delta variant. The paper was published in The Lancet Infectious Diseases.

A peptide vaccine in a Phase 1 clinical trial

A peptide vaccine, CoVac-1, generated good T cell responses against a range of variants of concern in a Phase 1 clinical trial. The vaccine consists of a range of viral proteins known to be recognised by T cell receptors. It is a single dose vaccine. The trial involved 36 participants, and the vaccine proved to have a good safety profile. The paper was published in Nature.

Non-vaccine-related papers

A new variant is making scientists nervous

A Nature news article summarises what is currently known about a new variant, B.1.1.529, that emerged in Southern Africa. It has a lot of mutations and appears to be highly transmissible. There is considerable uncertainty about whether it is able to avoid immune responses and vaccines.

The UK Science Media Centre has an Expert Reaction on this variant, and one in the US.

Increased transmissibility is the key to success for the virus

A model simulating the dynamics of viral variants suggests that new variants with some degree of immune escape are less likely to be a critical threat unless they also have higher transmissibility. This supports observations of the limited impact the more pathogenic Beta variant has had. It was less transmissible than the Alpha variant, and so did not supersede it, unlike the Delta variant.

The model also illustrated the benefits vaccination, and other public health measures, can have on limiting transmissibility and the consequences of infections. The model doesn’t take account of several variants circulating at the same time, or waning effectiveness of vaccines. The paper was published in Cell.

Another antiviral being tested

Thapsigargin, a broad spectrum antiviral, prevented replication of Alpha, Beta, and Delta variants in cell culture tests. It is derived from a poisonous Mediterranean plant called “deadly carrot”. The drug was also able to inhibit existing infections and block infections involving pairs of variants. It has previously been shown to help block influenza and RSV viruses. The paper was published in Virulence.

Infection lethality increased at the end of 2020 in the UK

Statistical modelling on infections in the UK found a two-fold increase in the Infection Fatality Rate in late 2020. Similar results were found for Germany and France. This increase in lethality preceded the spread of the Alpha variant. The authors conclude that the change in lethality may have been due to a combination of seasonal factors and pressures on the health system, rather than changes in the virus. The paper was published in PLOS ONE.

Distribution of earliest cases supports market as key source of outbreak

A perspective published in Science supports earlier conclusions that a significant number of the earliest cases of Covid-19 were associated with the Huanan Market in Wuhan, strengthening support for a natural spillover origin. While no live animals from the market (or others in the city) were tested for SARS-CoV-2 the author suggests that further analysis of the spatial distribution of early cases, and further genomic analyses, may help provide further evidence of Huanan Market being a primary source of the initial outbreak in Wuhan.

Limited knowledge about bat coronaviruses

A review of studies of bat coronaviruses identifies important knowledge gaps. These factors relate to spillover and pandemic risks, and include pathways to spillovers, infection dynamics in bat hosts, prior adaptation in intermediate hosts, and viral traits that can predict zoonotic and pandemic risks. It calls for better integration of scientific disciplines to improve the understanding of risks. The paper was published in Nature Reviews Microbiology.

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