Vaccine-related papers

Comparing different vaccine effectiveness against the Delta variant

A US study suggests that the Moderna vaccine may be more effective than the Pfizer/BioNTech vaccine against infection by the Delta variant. Analysing data from several states indicated that those receiving the Moderna vaccine appeared to be half as likely to become infected as those who had the Pfizer/BioNTech vaccine. Though both vaccines provide strong protection against infection and serious disease.

A variety of factors may lead to differences in effectiveness against infection between the two vaccines. Effectiveness based on time since vaccination was not assessed. The paper has not yet been peer reviewed.

A Qatari study of over 1 million vaccinated people also found that the Moderna vaccine was more effective against infection from the Delta variant than the Pfizer/BioNTech vaccine. Effectiveness against asymptomatic or symptomatic infection at least two weeks after the second dose was 53.5% for the Pfizer/BioNTech vaccine, and 84.8% for Moderna.

Both vaccines remained very effective against serious disease, with effectiveness of 89.7% for Pfizer and 100% for Moderna.

Most of the Pfizer/BioNTech vaccinees had been vaccinated about three months longer than those who received the Moderna vaccine. The authors suggest the results may reflect waning effectiveness. But other factors may also contribute to the lower effectiveness. The paper has not yet been peer reviewed.

Two doses are much better than one against the Delta variant

A single dose of either the Pfizer/BioNTech or AstraZeneca/Oxford vaccine was less effective against symptomatic disease for the Delta variant than the Alpha (30.7% for Delta, compared with 48.7%). However, differences in effectiveness against the two variants were less after the second dose (79.6% for Delta, compared with 87.5% for Alpha). The Pfizer vaccine had a higher level of effectiveness against Delta (88% vs 67% for AstraZeneca). The study is based on thousands of infections in the UK.

A limitation of the study is that there may be biases in who received which vaccine, when, and the interval between the doses, so comparisons of effectiveness between the two vaccines may be less reliable. The paper was published in The New England Journal of Medicine.

Vaccinated people who become infected can infect others

A Vietnamese study of 62 Delta variant breakthrough infections in vaccinated healthcare workers found that they were able to infect others. The workers had received the AstraZeneca/Oxford vaccine, but worked in poorly ventilated settings. It also found that the infections had viral levels 251 times higher than levels seen in Infections in 2020.

Infected vaccinated healthcare workers had lower levels of neutralising antibodies than uninfected matched vaccinated workers. However, neutralising antibody levels were not a good predictor of respiratory symptoms or viral loads.

Only one of the infected vaccinated workers studied required supplemental oxygen, and all recovered, indicating the vaccine’s effectiveness in preventing serious disease. The paper has not yet been peer reviewed.

Delta variants inhibit neutralising antibodies

The Delta, Delta+ and Kappa (B.1.617.1) variants dampen vaccine-elicited neutralising antibodies. The impact of the Delta+ was similar to that seen for the Beta variant. The paper also reports several monoclonal antibodies that target the spike protein N-terminal domain and cross react with several variants, which could inform new vaccine development. The paper has not yet been peer reviewed.

Moderna vaccine safe and effective for adolescents

A Phase 2/3 trial of the Moderna vaccine in adolescents (12-17 year olds) found it to be safe. Nearly 2,500 were vaccinated, with 1,200 others receiving a placebo. The immune response to the vaccine was similar to that seen in young adults. Four infections were seen in the placebo group, and none in the vaccinated group. The paper was published in The New England Journal of Medicine.

Two vaccine doses boost T cells, but only in uninfected vaccinees

T cells produced in response to mRNA vaccines respond in the same way to the spike proteins from the original SARS-CoV-2 strain and the Beta variant. Spike-specific T cells were boosted after the second vaccine dose in uninfected vaccinated people, while the second dose for those who had a previous infection did not further increase the T cell responses.  

The spike-specific T cells in the previously infected vaccinated group appeared to have features that may make them persist longer, and to be more effective at targeting the virus in the upper respiratory tract.

The authors consider that a second vaccine dose for those who were previously infected may have little effect, though this still requires further research. The paper has not yet been peer reviewed.

CD4+ T cells respond quickly to first mRNA vaccine dose

Rapid production of virus-specific CD4+ T cells are seen in uninfected individuals after receiving the first dose of either mRNA vaccine. In contrast, CD8+ T cells increase gradually. This result was interpreted to indicate that CD4+ cells may be able to prevent infection when antibody levels are low.

The dynamics of CD4 and CD8 cells differed between vaccinated uninfected and recovered Covid-19 participants. For recovered cases, the second vaccine dose had only a small effect on the T cell populations, in contrast to continued boosting in virus-naive participants. This mirrors results for antibodies.

The authors conclude that two doses of mRNA vaccines are necessary for those who have not been previously infected. The study also describes the coordination between the antibody and T cell parts of the immune response.

The study is limited by the small number of participants, and that only cases of mild Covid-19 were included. The paper was published in Immunity.

Vaccination can help reduce risk of viral mutations

Increased vaccination appears to reduce the risk of new viral mutations appearing in Delta variants. This is based on correlations of vaccination rates and mutation frequencies in 20 countries. Countries with higher vaccination rates tended to have  viral genomes with fewer mutations in June & July of this year.

The result is a correlation only, and the application (or lack) of non-pharmaceutical public health measures also seem to influence mutation frequencies. The paper has not yet been peer reviewed.

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Non-vaccine-related papers

Delta variant has a higher effective reproduction number

A Singaporean study found that the rapid spread of the Delta variant is more likely due to a higher effective reproduction number for the variant, rather than having a shorter generation time between infections. This is based on comparing times of transmission within households before and after the arrival of the Delta variant. The median serial interval between a household contact being infected by the primary case was 3 days in both cases. However, only small numbers of cases were studied. The paper was published in The Lancet.

Some cases of Long Covid linked to airway damage

Long Covid respiratory problems appear to be associated with higher levels of cytotoxic lymphocytes (and two other biomarkers) in the airways, resulting in increased cell death and damage. This abnormality was not found in peripheral blood, so blood sampling alone isn’t useful for diagnosis.

For patients in this study the problems within the airways appear to have gone within one year. The results won;t apply to those whose long lasting symptoms do not include respiratory difficulties. The paper has not yet been peer reviewed.

One third of infections may be asymptomatic

An analysis of hundreds of studies estimates that true asymptomatic infections make up 35% of all Covid-19 infections. At the time of testing nearly 43% may not show symptoms. Older people are less likely to have asymptomatic infections (19.7%), while nearly half of children (46.7%) may not develop symptoms.

The high proportion of asymptomatic cases in younger people poses challenges for reliably detecting cases and controlling transmission. Shifting definitions of symptoms makes it difficult to accurately estimate asymptomatic cases. The paper was published in the Proceedings of the National Academy of Sciences.

Large scale trials essential to find effective therapies

The very large World Health Organisation SOLIDARITY trial for testing the effectiveness of drugs against Covid-19 is starting up again. Discussions with pharmaceutical companies and gaining regulatory approvals delayed testing. Three drugs are about to enter the trial. All target the immune system rather than the virus, because the damage has already been done by the time people become hospitalised. More details are in a news item in Science.

A news item in Nature discusses the withdrawal of an influential paper that claimed the anti-parasitic drug ivermectin was an effective Covid treatment. It is alleged that some of the data was fabricated. The news article notes that the rapid rush to publish means that most studies of drugs as Covid-19 treatments are small, and so of very little validity.

Comparing antibody assays

An Australian study comparing six commercial antibody detection tests found that all are reliable enough to be used. There is variation in the specificities and sensitivities between the tests. Some of the tests may be more better than others when testing those who have already been vaccinated. The tests don’t measure neutralisation ability so do not provide a measure of immune protection. The paper was published in Open Forum Infectious Diseases.

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