Coronavirus Research Tracking - 23 July

Vaccine laboratory & real world effectiveness, antibodies longevity and targets, and potent new virus inhibitors

This week, more reports on the laboratory and real world effectiveness of different vaccines, poor countries missing out on vaccines, the antibodies that target SARS-CoV-2, and possible new therapies.

The tracker is now being shared with the COVID-19 Vaccine Media Hub, so vaccine and non-vaccine-related papers are more clearly highlighted.

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Vaccine-related papers

Sputnik V vaccine stimulates good antibody responses

An Argentinian study of 288 health care workers found that 94% develop antibodies 21 days after receiving the first dose of the Sputnik V vaccine. (The vaccine is a combination of two adenovirus vectors.) Antibody and neutralisation levels were higher in workers who had been previously infected and received one vaccine dose than in uninfected workers who had received both vaccine doses. The degree of real world protection following vaccination was not assessed. The paper was published in Cell Reports Medicine.

Coronavac vaccine may produce lower levels of neutralising antibodies than the Pfizer/BioNTech vaccine

A small Hong Kong study compared antibody responses to the Pfizer/BioNTech and Coronavac vaccine (an inactivated virus). Neutralising antibody levels were substantially higher following two doses of the Pfizer vaccine compared with Coronavac. This may lead to different effectiveness of protection, although this was not tested. The paper was published in The Lancet Microbe.

Johnson & Johnson/Janssen vaccine booster may be required for protection against Delta variant

The Johnson & Johnson/Janssen vaccine elicited lower neutralisation activity against the Beta, Delta and Lambda variants than the Pfizer and Moderna vaccines. Sera from mRNA vaccinated people showed an average three-fold lower neutralisation titre against these variants compared to an earlier isolate. The Johnson & Johnson vaccine showed five to seven fold decreases, which may result in decreased protection against infection.

Previous studies did not show a similar low level of neutralisation for the Johnson & Johnson vaccine (see the 9th July Tracker), which the authors suggest may reflect differences in the groups tested. The authors also suggest a booster shot of the Johnson & Johnson/Janssen vaccine may be helpful against the Delta variant. This paper has not yet been peer reviewed.

Two doses of Pfizer or AstraZeneca vaccines provide good protection against Delta variant

Two doses of the Pfizer/BioNTech and AstraZeneca/Oxford vaccines are much better than one for protection against the Delta variant. This large study from Public Health England, involving thousands of participants, found that the difference in effectiveness in preventing symptomatic infection against the Delta and Alpha variants was smaller after two vaccine doses than after just one.

After a single dose of either vaccine effectiveness against the Delta variant was 30.7%, compared with 48.7% against the Alpha variant. After two doses the differences were proportionally smaller. The Pfizer/BioNTech showed 93.7% effectiveness against Alpha and 88.0% against Delta. For AstraZeneca/Oxford, the effectiveness against both variants was lower; 74.5% against Alpha and 67.0% against Delta. The paper was published in the New England Journal of Medicine.

mRNA vaccines show great protection against infection in older people

A study of infections at US Veterans Affairs health care centres found that the two mRNA vaccines provided 97% effectiveness against infection. The study compared 54,000 infected participants with a matched group of 54,000 uninfected participants. The average age of participants was 61 years, and mainly male. The paper was published in the Annals of Internal Medicine.

mRNA vaccines boost particular B and T cells

mRNA vaccines boost spike protein-specific B cells and CD4 T cells, but not CD8 T cells. The study only involved four vaccinated and three unvaccinated participants with mild Covid-19. The paper has not yet been peer reviewed.

Second dose of Pfizer/BioNTech vaccine boosts innate immune response

The second dose of the Pfizer/BioNTech vaccine considerably enhances the innate immune response. After the first dose was given to 56 uninfected volunteers, type I interferon levels were very low, but increased substantially after the second dose. The higher levels of interferon were associated with higher and broader levels of transcriptional activity, in line with the hypothesis that type I interferons stimulate the production of other antiviral  and inflammatory responses. The paper was published in Nature.

Stronger neutralisation activity seen in people who have been infected and vaccinated

Neutralisation activity against a range of variants is stronger in vaccinated people who had recovered from Covid-19 than in vaccinated people who had not been infected. This was despite similar levels of neutralising antibodies after the second vaccination.

For variants with the E484K and N501Y/T mutations (such as Beta and Gamma) neutralisation activity was around 10 fold lower in vaccinated but uninfected participants, compared to an earlier “wild type” variant. For the Delta variants (several are now recognised) the decrease in neutralisation activity was about 6.5-fold, which appears at least in part attributable to the L452R mutation.

This study differs from previous ones in that it used complete viruses, rather than fragments of them to assess neutralisation activity. Participants had been vaccinated with either the Pfizer/BioNTech or Moderna vaccines. The paper has not yet been peer reviewed.

Medsafe warning about rare heart risk from Pfizer/BioNTech vaccine

New Zealand's Medsafe, in-line with other medicine regulators, has noted that myocarditis (inflammation of the heart muscle) is a rare adverse reaction associated with the Pfizer/BioNTech vaccine. It notes that myocarditis is hard to distinguish from pericarditis (inflammation of the sac around the heart) so it is also included as part of the warning. Medsafe emphasises that the benefits of vaccination continue to outweigh the risks.

Poorer countries may not get vaccines for years

A news item in Nature reports that Covid-19 vaccines won’t reach many of the world’s poorest countries until 2023, based on current commitments by wealthier countries.

Non-vaccine related papers

Mutation in Delta variant associated with higher infectivity and pathogenicity

The P681R spike protein mutation, seen in the Delta variant, leads to higher levels of virus-cell fusion. This mutation is also associated with greater pathogenicity. Infecting Syrian hamsters with the Delta variant resulted in greater pathogenicity, compared with hamsters infected with a B.1.1 strain. This paper has not yet been peer reviewed.

Long lived antibodies found in Italian study

An Italian study found that virtually all (98.8%) of people with SARS-CoV-2 antibodies in May 2020 still had them in November. Often antibody levels remained stable over these seven months. In a few cases increases in antibody levels and neutralisation activity was found to be associated with asymptomatic reinfection, indicating that the earlier immune response was able to prevent disease but not completely stop viral replication. 

Secondary infections within households were found to be very variable. The authors suggest that due to this variability contact tracing needs to be combined with mass testing to control outbreaks.

The study also found that different antibody tests did not yield the same results, with one (the Abbott assay) probably underestimating infections. The paper was published in Nature Communications.

Key antibodies against SARS-CoV-2

Some of the antibodies that target SARS-CoV-2 and viral mutations that provide resistance to them are nicely illustrated in a short article published in Cell Host & Microbe.

CRISPR used to inhibit SARS-CoV-2

Genetic editing using the CRISPR system has allowed mammalian cells to prevent replication of SARS-CoV-2. RNA molecules were produced using this system that can bind to the viral spike or nucleocapsid RNAs, which then leads to their degradation. These engineered RNAs are able to bind to the viral RNA from several variants of concern, indicating that the system may be able to target a variety of variants. Experiments were performed in monkey and human cell cultures. 

A safe and efficient method of delivering the CRISPR RNA into people still needs to be developed, and application is probably years away. The authors note that the CRISPR system has the benefits of design flexibility and adaptability, and is suitable for tackling a variety of infectious diseases. The paper was published in Nature Communications.

Potent inhibitor of coronaviruses found

A tyrosine kinase inhibitor appears to be very effective at stopping the replication of SARS-CoV-2 and other coronaviruses. The drug, called Masitinib, reduced viral concentrations in mice by more than 200-fold, and was able to inhibit current variants of concern in cell tests. Clinical trials are still required. The paper was published in Science.

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