Coronavirus Research Tracking - 4 December
Genomics, new vaccines, rapid tests, mucosal immunity
This week’s Research Tracker has a focus on genome studies and repurposing older vaccine systems. Also, a paper about a neglected area of immunity research.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Flight detectives
A study by New Zealand’s ESR (available as a pre-print) looked at the patterns of infection among seven people from different countries travelling to NZ on the same flight. Seventy nine other passengers on the flight did not become infected. Using genome sequencing, timing of symptom development and travel itineraries they concluded that at least four of the travellers became infected during the flight directly or indirectly from a passenger coming from Switzerland.
Spread of a new variant across Europe
The rapid spread of a viral variant from Spain across Europe is reported in a pre-print paper. The frequency of the variant increased during the northern autumn, but the researchers conclude that this was not due to a selective advantage. Instead, increased travel during summer, and lack of effective screening and containment appear responsible for its growing prevalence.
Six strains of SARS-CoV-2 identified
Analysis of genomes, reported in Proceedings of the National Academy of Sciences, has identified six strains of the virus. These can be distinguished by 14 single nucleotide variations across the virus. One strain, called type VI, has become dominant, making up over 72% of the sequenced genomes. The authors suggest that type VI has a selective advantage, but that they do not know what the advantage may be.
The analysis also shows that not all lineages carrying the frequently mentioned single base D614G variant persist. So, by itself this mutation does not seem to provide a selective advantage, and this may explain the ambiguous evidence for greater infectivity associated with it. The authors note that other mutations elsewhere in the genome also need to be considered to explain the frequency of variants with the D614G change.
Speed beats sensitivity in community testing
Speed can beat sensitivity when screening for infections within communities. Test sensitivity is the ability of a test to correctly identify those with the virus. A modelling study, published in Science, found that frequent screening and fast reporting of results can be more important than the use of highly sensitive tests in helping control infection spread. This is because the levels of virus change rapidly during the early stages of infection, so more frequent testing can pick up these changes. The authors recommend that more tests need to be approved for community use.
You can have both speed and accuracy
Rapid tests don’t necessarily sacrifice accuracy. A paper (not yet peer reviewed) compared the sensitivity of three commercial rapid antigen diagnostic tests with PCR tests on saliva and nasopharyngeal swabs. More than 900 infected people were tested. It found that the sensitivity of the rapid tests was relatively high, over 85% when compared with nasopharyngeal PCR tests. This increased to over 90% when viral loads were high (more than a million copies per ml).
All three rapid tests had 100% specificity, meaning they did not identify uninfected samples as being infected. It is important to stress that not all rapid tests will be so accurate, so rapid tests need to be chosen with care.
A paper in Nature Biomedical Engineering describes a portable PCR test that can provide results in 17 minutes. It detects viral RNA using nanoparticles and fluorescence, and correctly identified 75 infected and 75 uninfected people.
Re-infections still a rarity
A news site is keeping track of re-infection cases. They list 26 confirmed cases between August and November, and nearly 1,000 suspected cases. Over 200 re-infections have been reported, but not confirmed, in Brazil, Mexico, and in Qatar (the news site has under-reported Qatar’s cases).
Many re-infections are probably overlooked, or can’t be confirmed because of lack of genetic evidence. Between August and November the cumulative number of global infections rose from 17 to 62 million, so re-infections appear to be very rare in the first nine months of the pandemic.
Repurposing vaccines
The pace of vaccine development isn’t slowing down. A range of vaccines built off pre-existing ones are in clinical trials (such as the BGC vaccine, and the AstraZeneca/Oxford vaccine). Animal trials using three existing viral vaccine vectors were reported this week.
A Covid-19 vaccine based on the live attenuated measles virus vaccine shows promise. The results, published in the Proceedings of the National Academy of Sciences, inserted the spike protein into the virus. Tests of one of the resulting vaccines in mice demonstrated the production of antibodies and T cells against the spike protein. Further tests on mice and hamsters infected with SARS-CoV-2 resulted in lower viral loads, and less lung damage in hamsters.
Using the measles vaccine provides a means to simultaneously vaccinate against both Covid-19 and measles, which is an important consideration due to lower vaccination rates in general during the pandemic.
A paper in Nature Communications describes a Covid-19 vaccine based on a widely used poxvirus vaccine vector, a DNA vaccine. Mice injected with the vaccine containing both the SARS-CoV-2 spike and the nucleocapsid protein sequences developed strong antibody and T cell immune responses. Only four to five mice were injected for each trial, so further research is required.
Developing such multi-antigenic vaccines decreases the likelihood of vaccine resistance developing.
A paper in Nature describes a Covid-19 vaccine based on the yellow fever virus. The yellow fever virus vaccine is known to be very safe for people. A single dose of this live virus vaccine containing the SARS-CoV-2 spike protein antigen was injected into mice, hamsters and macaques. It produced high levels of neutralising antibodies in treated animals. Injected mice also developed a T cell response to the vaccine, indicative of good immunity.
Hamsters, which are very susceptible to SARS-CoV-2, did not develop lung disease if they were vaccinated before infection. The vaccine protected mice and macaques from infection. Protective immunity was seen within 10 days of vaccination, much quicker than seen for two-dose vaccines, such as Pfizer’s and Moderna’s. Clinical trials on people have yet to commence.
Will immunity from vaccination be stronger than from natural infection?
A letter in Nature Medicine discusses whether immunity from a Covid-19 vaccine will be stronger than immunity from a natural infection. The authors note that there are cases where a vaccine generates a stronger response than natural infection, such as for the human papillomavirus and shingles vaccines. In other cases, natural infections lead to stronger immunity.
It is still unclear how strong immunity to Covid-19 vaccines will be, but the authors are optimistic, based on animal trials, that some vaccines are likely to provide better immunity than a SARS-CoV-2 infection.
Success at last for “nanomedicines”
An article in Nature Nanotechnology discusses the significance of the mRNA vaccines BNT162b2 (from Pfizer/BioNTech) and mRNA-1273 (Moderna) in relation to what the authors call “nanomedicine.” This is is the use of very small molecules or particles for therapeutic uses. The article reports that nanomedicine approaches, especially for cancer therapies, have often led to underwhelming results when translated from the pre-clinical to the clinical arena. This is due to the complex and still poorly understood nature of the nanoscale interactions in biology.
The encouraging results for these vaccines, the authors suggest, offers promise too for other nanomedicine approaches.
Monoclonal antibodies may be effective against both milder and more severe Covid-19
The effectiveness of two monoclonal antibodies is reported in Science. The antibodies target the spike protein, and are used together to reduce the chance of viral mutations reducing protection. This “cocktail” (REGN-COV2) was tested on rhesus macaques and golden hamsters, both before and after being infected with SARS-CoV-2.
Macaques develop milder symptoms while hamsters are more seriously affected by the virus. In macaques while the antibodies didn’t prevent infection they reduced both viral levels and lung damage. In treated hamsters viral levels were also reduced and they suffered less weight loss than untreated infected animals. However, only five to six animals were used for each test.
Mucus membranes - a neglected area of immunity research
An article in Frontiers in Immunology highlights that most studies of immune responses to SARS-CoV-2 study blood or sera. However, they note that the mucosal immune system (the mucus linings of the respiratory and digestive tracts) is the biggest component of the overall immune system and has a central role in responses to respiratory viruses. The authors also point out that more attention needs to be given to secretory antibodies, produced by the upper respiratory tract.