Coronavirus Research Tracking - Vaccine Edition - 20 May
vaccine comparisons, 4 vaccine doses, new vaccines
This week, comparing immune responses from different vaccines, reduced risk of long Covid after vaccination, immune response to Omicron after being vaccinated, a clinical trial for four vaccine doses, vaccination of immunocompromised patients, and new vaccines being developed.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
mRNA vaccines generate stronger immune responses than adenovirus-based ones
In direct comparisons a Dutch study found that mRNA Covid vaccines generated stronger neutralising activity against variants of concern than adenovirus-based ones. Peak neutralisation activity was seen about 4 weeks after initial vaccination series (1 or 2 doses). A booster dose of the Pfizer/BioNTech vaccine increased neutralisation activity for all vaccine groups. The authors note that immune factors besides neutralising antibodies contribute to protection, and these were not assessed in their study.
The study involved 165 vaccinated healthcare workers with no Covid-19 infections. The age profiles differ between the different vaccine groups, which may influence the results. The paper was published in PLOS Medicine.
Vaccines can reduce risk of long Covid symptoms
Vaccination after an infection was associated with reduced risks of long Covid. Persistence of long Covid for at least 12 weeks was the focus of the study. After one dose the odds of experiencing long covid symptoms decreased by an average of 13%, while after a second dose there was an additional 9% reduction. The authors suggest that the vaccines may help ‘reset’ a dysregulated immune system, but this requires further research.
Participants received either mRNA vaccine or the AstraZeneca/Oxford vaccine. Nearly 16,000 people participated in the study, with just under 7,000 reporting long Covid symptoms. The study involved random sampling, so reducing bias, but symptoms were self-reported. The paper was published in the BMJ.
Catching Omicron after vaccination can boost the immune response
Without vaccination, infection with Omicron induces a limited humoral immune response. Sera from Omicron-infected mice only neutralised Omicron, while those infected with wild-type or the Delta variant showed broader neutralisation activities. This was also seen in humans. When vaccinated with Pfizer/BioNTech and then infected with Omicron there is stronger neutralisation activity against the variants than seen just for vaccination.
Small numbers of mice and people were involved in the study. The paper was published in Nature.
Pfizer vaccine generates T cells that can target BA.1
T cells generated by the Pfizer/BioNTech vaccine are able to target the Omicron (BA.1) variant. A prior infection followed by two vaccine doses substantially increased the percentage of polyfunctional T cells that were able to target the wild type and Omicron variant. The paper was published in Nature Microbiology.
Four vaccine doses boost antibody and T cell responses
A Phase 2 randomised trial found that a fourth vaccine dose boosts cellular and humoral immunity, and does not generate serious adverse reactions in older people. One of the mRNA vaccines was given as the fourth dose, with Pfizer/BioNTech given as a full dose (30 μg in 0.30 mL), and Moderna’s vaccine as a half dose (50 μg in 0.25 mL). Participants had previously received either the Pfizer or AstraZeneca vaccines as the first two doses, followed by a Pfizer dose.
Two weeks after the fourth dose IgG antibody levels had increased 12-to-15 fold compared to just before the dose. T cell responses were boosted 6-to-7 fold, although this was based on a smaller sample size.
Peak IgG levels were higher than seen at one month after the third dose. The half dose Moderna shot gave a larger immune boost than the full dose Pfizer, which may be at least partly due to participants not having had earlier Moderna doses.
The fourth dose was given about 7 months after the third. The median age of participants was 70 years. Numbers in each vaccine combination group were relatively small, and comparisons of 3rd and 4th doses were done at different time points. Neutralising antibody activity was not measured, but is expected to correlate with binding antibody levels. The paper was published in The Lancet Infectious Diseases.
Three vaccine doses improve immune responses in immunocompromised patients
Two doses of mRNA vaccines in immunocompromised patients generated low levels of antibodies, which often became undetectable six months later. A third vaccine dose provided a significant antibody boost, and the results indicate it should be given less than six months after the second dose.
Participants had a variety of diseases, and immune responses to the vaccines differed by disease type. Cancer (multiple myeloma) patients had the poorest responses to the vaccines.
Patients with solid tumours or cancer developed stronger immune responses when they received the Moderna vaccine rather than the Pfizer, but there was little difference between vaccine types for those with inflammatory bowel diseases.
The authors recommend creating individualised vaccination schedules for immunocompromised patients. The paper was published in Frontiers in Immunology.
New live-attenuated virus vaccine shows promising results in hamsters
A live-attenuated virus vaccine generated stronger immune responses and viral clearance in hamsters, compared with the Pfizer/BioNTech and Johnson & Johnson/Janssen vaccines. Immune responses were especially strong at mucosal sites (the usual sites of viral infection).
The attenuated virus vaccine also improved immune responses when given three weeks after the Pfizer vaccine. Further research and development on the vaccine is under way. The paper has not yet been peer reviewed.
New T cell based vaccines
Using new vaccines on mice, this study found that T cells can limit viral replication in lungs, even when the virus evades neutralising antibodies. The vaccines were adjuvanted spike protein–based and designed to generate strong T cell responses.
The authors advocate for development of T cell-based vaccines that could provide good protection against future variants. The paper was published in the Proceedings of the National Academy of Sciences.