Coronavirus Research Tracking - 21 May
Vaccine effectiveness, pan-coronavirus vaccines, antivirals, predictors of outcomes, improving surveillance
The mRNA vaccines continue to demonstrate their effectiveness and safety. Several research teams are hoping to create a broad spectrum coronavirus vaccine. Two promising quick acting antivirals are in pre-clinical trials. Blood profiles and T cell dynamics may help predict disease outcomes. Global virus surveillance needs improving.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
mRNA vaccines continue to prove themselves
Another study has shown the real world effectiveness of the Pfizer/BioNTech and Moderna vaccines. In a group of US nursing homes with thousands of residents, infections declined both in vaccinated as well as unvaccinated residents after vaccinations commenced. A greater proportion of the vaccinated residents had asymptomatic infections, compared to unvaccinated residents. Published in the New England Journal of Medicine.
Indian variants don’t appear to escape vaccines
The B.1.617 and B.1.618 variants are probably still able to be controlled by the two mRNA vaccines. This is the conclusion of a study where the spike proteins of these variants were introduced into a pseudovirus and tested against sera from convalescing Covid-19 patients and vaccinated people. There was only a modest decline (three to four-fold) in neutralisation activity against these variants compared to wild-type virus. The paper has not yet been peer reviewed.
Similar results were reported in another study. Antibodies generated by the Pfizer/BioNTech and Moderna vaccines can be seven times less effective at blocking the B.1.617.1 variant, compared with an earlier strain. However, the variant was still able to be neutralised to some extent. And sera from unvaccinated convalescent people was often able to neutralise the variant as well.
The study involved only 25 vaccinated people. However, it tested the actual virus rather than a pseudovirus, so the results are more likely to reflect real infections. The study has not yet been peer reviewed.
Delaying second dose could benefit older people
People over 80 may benefit from delaying the second Pfizer/BioNTech dose. Peak antibody levels were 3.5 times higher in uninfected participants who received the second dose at 12 weeks rather than 3 weeks after the first dose. However, cellular immune responses were stronger in those who had the second dose at 3 weeks. The participants need to be monitored further to see what the long term immunity and protection effects are. The paper has not yet been peer reviewed.
Mix-and-match vaccination may have benefits
Preliminary results from a mix-and-match vaccine trial indicate that receiving a vaccine mix can be beneficial. The results are not yet published, but are reported on in a Nature news article. A Pfizer/BioNTech dose substantially boosted antibody responses after participants received a shot of the AstraZeneca/Oxford vaccine. Last week’s tracker reported on another trial that found a mix-and-match approach increased minor adverse reactions, but not serious reactions.
Vaccination still looking safe for pregnant women
A study of 84 vaccinated (with the Pfizer/BioNTech or Moderna vaccines) pregnant women did not find any adverse effects on the foetus or the placenta. The paper was published in Obstetrics and Gynecology.
Vaccinated pregnant and lactating women were found to produce binding and neutralising antibodies in infant cord blood and breast milk. There were no reports of serious adverse reactions or complications to the vaccines. Thirty pregnant and 16 lactating women participated in the study, which was published in JAMA.
Vaccination boosts antibody memory cells and corrects dysfunctions
After infections and vaccinations neutralising antibodies decline, but the memory cells that create them persist (for at least 8 months). Vaccination with mRNA vaccines stimulated stronger antibody responses and memory cell populations than natural infections, indicating that vaccinations may lead to longer term protection. Memory B cells were boosted more in vaccinated people who had previously been infected than uninfected vaccinated people.
In addition, vaccination was found to correct an immune dysfunction, where faulty B memory cells accumulate after an infection. The paper is not yet peer reviewed.
Potential for pan-coronavirus vaccines
Three recent papers suggest the feasibility of a more general coronavirus vaccine.
A nanoparticle vaccine with a receptor binding domain sequence stimulated neutralising antibodies in macaques that were effective against a range of coronaviruses, including SARS-2-CoV-2 variants of concern. It prevented the virus from replicating in the lungs and nose. To a lesser extent the Pfizer/BioNTech vaccine elicited cross neutralising antibodies. Only a small number of macaques were tested. The paper was published in Nature.
A strongly conserved target for T cells was found in the receptor binding domain that. This is found in not only variants of concern, but other coronaviruses too, opening the possibility of a universal coronavirus vaccine. This target wasn’t obvious from sequence analysis alone. The paper was published in Science.
A pan-SARS-CoV-2 vaccine, INO-4802, produced potent neutralising antibody and T cell responses against a range of variants of concern in preclinical trials. The vaccine was created by analysis of spike protein sequences and design of a common set of overlapping mutations. When tested in mice good responses were seen against wild-type SARS-CoV-2, B.1.1.7, P.1, and B.1.351.
In hamsters, a strong antibody response was seen when INO-4802 was used as a booster eight months after vaccination with a vaccine designed for the wild-type virus. The paper has not yet been peer reviewed.
A T cell test to identify exposure
A new test for long-lived T cells may be a useful complement to antibody testing to identify previous infections and to study vaccine effectiveness. The test is described in a news article in Nature Biotechnology.
P.1 variants created through sequential infections
Analysis of a P.1-like variant concludes that the set of mutations seen in P.1 developed from sequential infections, rather than within a single immuno-compromised individual. The authors conclude that partial immunity which developed from infections early in 2020 may have led to selection for subsequent mutations. Human behaviours, not just greater infectivity, also appear to have contributed to the spread of P.1. The paper has not yet been peer reviewed.
Promising new antivirals
A chemical that activates interferon genes was found to protect mice from Covid-19 when delivered intranasally before or after infection. The compound stimulates short term activation of type I interferons and cytokines that help stop viral replication. The treatment may also prove useful for other respiratory pathogens. The paper was published in Science Immunology. A companion paper in the same issue describes the pathway of action of a variant of this compound in cell lines.
Small-interfering RNAs encased in lipid nanoparticles have also shown very good effectiveness in inhibiting viral replication in mouse trials. These double-stranded RNA particles prevent the expression of specific viral genes. The therapy is injectable but the effect lasts only about 48 hours, so a series of treatments may be required. Only small numbers of mice have been tested so far. The study was published in Molecular Therapy.
Pre-existing use of anti-inflammatories doesn’t affect Covid-19 outcomes
Concerns that existing use of non-steroidal anti-inflammatory drugs could make Covid-19 worse have been dispelled by a large UK study. It matched (by age, gender and medical history) over 4,000 patients with Covid-19 with 4,000 patients who weren’t taking the anti-inflammatories and found that there were no differences in the proportions requiring critical care or who died due to Covid-19. The most common anti-inflammatory in the study was Ibuprofen. The study was published in The Lancet Rheumatology.
Blood signatures for Covid-19 severity
Analysis of a variety of molecules in the blood of Covid and non-Covid patients was able to identify blood signatures linked to different degrees of Covid-19 severity. Particular immune cell populations, and components of the immune and inflammatory responses are associated with different degrees of disease severity. The results may help identify patients that go on to develop more severe Covid-19. The paper has not yet been peer reviewed.
T cell timing is a predictor of disease outcome
A 12 week study of immune responses in 207 Covid-19 patients found that the timing of particular T cell responses and degree of inflammation were good predictors of disease outcome. Viral load did not correlate with initial symptoms but did for later disease severity. The study was published in Immunity.
Digital contact tracing often exceeded expectations
Digital contact tracing has been more effective than anticipated in many countries. That’s a conclusion from a perspective in the New England Journal of Medicine. It also notes that more needs to be done to integrate it into broader contact tracing procedures, and to ensure that it becomes more accessible for, and trusted by, everyone.
A detailed analysis of the impact the UK’s NHS Covid-19 app had on infections is described in a paper published in Nature.
Need to improve global surveillance
An editorial in Nature Biotechnology emphasises the need for greater coordination of SARS-CoV-2 surveillance and tracking internationally. While affluent countries have been improving their efforts, surveillance is often lacking in poorer countries. As vaccination gathers pace there is also the risk of increasing complacency about testing, at the same time as the need to monitor variants is becoming more important.
Outside of South Africa there is limited knowledge of viral variants circulating in Africa. A new study has looked more closely at other parts of Africa and identified strong connections between variants there and Europe. The rapid spread of the B.1.351 variant to other African countries also indicates that border controls within Africa are ineffective. Two variants of interest, B.1.525 in West Africa and A.23.1 in East Africa, are increasing in frequency and require further surveillance and study. The paper has not yet been peer reviewed.
The pandemic changed social sciences
The pandemic has had a big impact on how social scientists study human behaviour. There is now a greater emphasis on “big science”, using apps and the internet to recruit participants or collect data, and to change the design of studies. Examples are provided in a Nature news article.