Coronavirus Research Tracking - 16 September
Nasal vaccines, vaccine combinations, 4 dose effectiveness, long Covid, future preparedness
This week in vaccine research, several papers on nasal vaccines, immune responses to different vaccines including bivalent vaccines, the effects of three and four doses, and another potential universal vaccine.
In non-vaccine research, potential long Covid causes, prevalence, and similarities with ME. The effects of Covid on the immunocompromised. And, another report on lessons for dealing with future pandemics.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Nasal vaccines
A Danish study found that a vaccine dose delivered nasally into hamsters provides better protection against infection, compared with two intramuscular doses. Before the nasal dose the hamsters had received an intramuscular dose of it as well. Viral load in the upper respiratory tract was significantly reduced after the intranasal dose. It also found that transmission to other hamsters was reduced, compared with unvaccinated infected animals.
A subunit vaccine was used. The pattern of infection in hamsters is similar to that in humans. The effect on transmission after an intranasal dose was not compared directly to hamsters given two subcutaneous doses. Only small numbers of hamsters were used in each test. The paper was published in eBioMedicine.
Intranasal vaccination in mice led to longer term T cell responses and broader neutralising antibody activity than subcutaneous vaccination. A subunit vaccine was also used in this study. Only small numbers of mice were involved in the experiments. The paper has not yet been peer reviewed.
Following an infection IgA antibody responses in nasal mucosa differ from serum responses. Nasal IgA provides a first line of defence against infection. After a SARS-CoV-2 infection nasal IgA persists for about 9 months. However, unlike serum IgA and IgG, and nasal IgG, it isn’t restimulated by vaccination.
The authors suggest that intramuscular booster vaccinations are likely to have little effect on nasal igA levels. The study involved 446 adults with Covid-19. The paper has not yet been peer reviewed.
Immune responses to different vaccine combinations
An Argentinian study compared immune responses to 16 different combinations of five vaccines. Heterologous vaccine combinations usually generated stronger immune responses, with the order of the vaccines having a strong effect. The highest antibody levels were generated when the Moderna vaccine was the second dose. Different combinations generated different B and T cell profiles.
Two vaccine doses were given, with the Moderna, AstraZeneca, CanSino, Sputnik 26, Sputnik 5, and SinoPharm’s vaccines being tested. Just under 500 adults participated, with 20-to-40 in each combination group, Not all groups had the same time interval between first and second doses. The paper has not yet been peer reviewed.
Testing bivalent mRNA vaccines on mice
Omicron-based bivalent mRNA vaccines given as a third dose boosted immune responses in mice. The bivalent vaccines (based on Moderna’s, and containing the Wuhan and either the BA.1 or BA.4/5 spike protein) generated a broader set of neutralising antibodies than vaccines with only one spike protein.
Mice receiving the bivalent vaccine were slightly more resistant to a BA.5 infection, and had reduced lung damage, compared with mice who received a third dose of the Moderna vaccine.
Small numbers of inbred female mice were used. The paper has not yet been peer reviewed.
Bivalent SARS-CoV-2 and influenza vaccine
Another study developed bivalent vaccines that provided protection against SARS-CoV-2 and influenza. Vaccines, based on a vesicular stomatitis virus, were created with Delta spike protein sequences, along with a highly conserved part of an influenza virus. They reduced viral loads in both mice and hamsters infected with the Delta variant and H1N1 and H3N2 influenza viruses.
Vaccinated animals infected with the Delta variant experienced less weight loss and recovered more quickly than unvaccinated animals. When given high doses of H1N1 or H3N2, all vaccinated animals survived and had only moderate weight loss, while some unvaccinated animals died, and survivors lost more than 20% of their body weight. Intramuscular and intranasal administration of the vaccines gave similar results. The paper was published in Journal of Virology.
Immune responses to different vaccine types
A study reports that different vaccine types elicit different immune reactions. It compared antibody and T cell responses of two recombinant adenovirus-based Covid vaccines (AstraZeneca’s and Johnson & Johnson’s) and three mRNA vaccines (Pfizer, Moderna, & CureVac).
The mRNA vaccines stimulate Natural Killer T cells, platelets activation, and chemokine signalling pathways. The adenovirus vaccines negatively regulate CD4+ T cells, leukocytes chemotaxis, Interleukin-18 signalling, and antigen presentation
Small numbers of participants received some of the vaccines, and participants were able to choose which vaccine they received as a third dose. The paper has not yet been peer reviewed.
Three vaccine doses help some immunocompromised people
A randomised trial involving immunocompromised patients found a third vaccine dose can generate antibodies after two mRNA doses failed to. Forty one percent produced antibodies after the third dose. Participants who received a third mRNA dose produced higher antibody levels than those who received a different (AstraZeneca) dose.
No significant adverse effects following a third dose were reported. The study involved 51 adults receiving immunosuppressants who had not seroconverted after two vaccine doses. The paper was published in Nature Communications.
Four vaccine doses can benefit the over 80’s
A Singaporean study found a fourth mRNA vaccine dose improved protection against BA.5 for those over 80. The fourth dose was given at least five months after the third. Compared with those who had three doses, vaccine effectiveness after four doses was 22% higher against infection, 55% higher against hospitalisation, and 63% higher against severe Covid-19.
Forty thousand elderly people who had received four doses were compared with 40,000 who had received three doses. The effects of other Covid treatments or comorbidities were not examined. The paper was published in Annals of Internal Medicine.
Another potential pan-coronavirus vaccine in development
Non-clinical trials of a self-replicating vaccine show promise as a pan-coronavirus vaccine. The temperature controllable self-replicating RNA vaccine contains spike protein sequences as well as more conserved viral nucleoprotein sequences from SARS-CoV-2 and MERS-CoV.
The vaccine is given intradermally and is activated at 30-35 oC (skin temperature), and deactivated at 37 oC. It is intended to be used as a booster since it is designed to activate T cells rather than antibodies.
The vaccine stimulated cellular immunity in mice. Further research is needed to develop and test the vaccine. The paper has not yet been peer reviewed.
Non-vaccine-related papers
Persistent viral antigens associated with some Long Covid cases
A small study found that viral antigens can persist in the blood of some people with long Covid for up to a year. They were not detected in people who fully recovered from their infection. This suggests some long Covid patients may have viral reservoirs.
The spike protein was the most commonly detected antigen, with others sometimes occurring too, potentially indicating different rates of degradation of viral proteins.
The study involved 37 adults with long Covid symptoms, and 26 with acute Covid-19. Only two of those with long Covid were hospitalised. The study does not demonstrate that viral reservoirs cause long Covid, and further research is necessary. The paper was published in Clinical Infectious Diseases.
Long Covid prevalence
A US study estimated that 21.5% of those with Covid had symptoms lasting more than four weeks. The survey was conducted in late June, and the BA.5 subvariant was becoming dominant during this time. Seventeen percent of the 3,000 people surveyed reported having had an infection in the previous two weeks. This is a much higher proportion than national official estimates, which are based on nucleic acid tests. Infections were more common in 18-to-24 year olds and those from disadvantaged communities.
The survey method may lead to biases in who responded. Symptoms were self reported. The paper has not yet been peer reviewed.
Long Covid & ME
Following on from a paper in the 2 September Tracker, the overlap in some long Covid symptoms and Myalgic encephalomyelitis is discussed in Science. The lack of good biomarkers, tests, and animal models for long Covid and ME makes it difficult to confirm and compare the conditions.
Covid in Immunocompromised people
A review of Covid-19 in immunocompromised people notes that a large proportion develop persistent infections. Due to the diversity of symptoms that an infection may generate there is no optimal treatment strategy for immunocompromised patients.
Further research on vaccine effectiveness for immunocompromised people is still required, particularly for newer variants. And other treatment options are still required. The paper was published in Immunity.
Lessons from the pandemic
A Commission created by The Lancet to identify pandemic lessons for the future has published its report in The Lancet. It highlights multiple failures in international cooperation in addressing the Covid-19 pandemic.
An associated editorial in The Lancet summarises the key points. It also notes that originally the Commission had a task force to identify the current pandemic’s origins, but this was shut down over disagreements between task force members. The report therefore doesn’t provide new evidence about origins.
However, the Commission's Chair has attracted controversy by sharing his unsupported views on the pandemic's origin with interviewers who promote pandemic mis- or disinformation.