Oral aerosolised COVID-19 booster creates high antibody levels

26th May 2022

An oral aerosolised COVID-19 booster dose elicited significantly higher serum antibody levels than those obtained via the intramuscular route

Use of an oral aerosolised COVID-19 booster has been shown to provide significantly higher mean serum antibody titres than those produced after a standard intramuscular dose according to the findings of a study by a group of Chinese researchers.

Evidence of a waning antibody response to COVID-19 vaccines has prompted the need for a booster dose. Moreover, there is good evidence to show that confirmed COVID-19 infection and severe illness are substantially lower among individuals who receive a booster dose.

The booster dose can either be homologous (i.e., the same as the primary vaccination) or heterologous, in which case the primary and booster are different. In practice, studies show that heterologous boosting results in a more robust immune response than homologous boosting and that this might enhance protection.

In addition to intramuscular vaccines, an oral aerosolised COVID-19 vaccine which encodes for the same spike protein has also been developed. In a phase I study, the oral aerosolised vaccine was found to be well tolerated and after two doses, elicited neutralising antibody responses, similar to one dose of an intramuscular injection.

However, what is uncertain, is the safety and immunogenicity of the oral aerosolised vaccine when used as a booster after two intramuscular doses.

For the present study, the Chinese team undertook a randomised, open-label, controlled trial in patients primed with two doses of the CoronaVac vaccine in the previous 3 – 9 months. Enrolled participants were randomised 1:1:1 to either a low or high dose heterologous booster or a homologous third dose with CoronaVac.

For the low and high dose vaccine, participants orally inhaled the aerosolised vaccine droplets. The primary endpoint for safety was the incidence of adverse reactions within 14 days of the booster dose and the primary endpoint for immunogenicity was the serum geometric mean titre (GMT) of antibodies against live COVID-19 virus 14 days after the booster dose.

Oral aerosolised booster dose effectiveness

A total of 420 participants with mean age of 40.7 years (42.6 % male) were randomised between the three groups and the median time between the second and booster dose was 5 months.

Adverse events were reported by 19% (low dose group) 24% (high dose group) and 39% in the intramuscular group (p < 0.0001). The most common adverse effects in the oral aerosolised groups were fatigue (13% low dose vs 11% high dose), followed by headache (8% low group vs 9% high dose) and fever (6% both groups).

Interestingly, the serum antibody levels generated by both oral groups were significantly higher than via the intramuscular route. For example, in the low dose group, the mean GMT was 744.4, 714.1 in the high dose group and only 78.5 in the intramuscular dose (p < 0.0001).

Based on their findings, the authors concluded that heterologous boosting with the oral aerosolised COVID-19 vaccine was safe and highly immunogenic, producing significantly higher antibody levels compared to a dose administered via the intramuscular route.

Citation
Li JX et al. Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial Lancet Respir Med 2022

Third booster sera samples have reduced neutralisation against Omicron COVID-19 variant

22nd December 2021

Third booster sera samples have been found to produce a four- six-fold decrease in neutralisation when tested against the Omicron variant

In a laboratory-based study, third booster sera samples from patients have been shown to produce a four to six-fold reduction in neutralisation against the Omicron COVID-19 variant. This was the finding of a preprint study by researchers from the Aaron Diamond AIDS Research Center, New York, US.

The Omicron COVID-19 variant (B.1.1.529) was first identified in southern Africa and appears to have a high level of transmissibility and will likely cause outbreaks across the globe. A concern with this particular variant is that it contains more than 30 mutations,15 of which are present in the receptor-binding domain region which is the target for neutralising antibodies produced in response to vaccination. It is therefore possible that the Omicron might lead to an increased level of infection despite vaccination although current opinion is that this could be mitigated by a third booster sera sample.

In the absence of clinical data, the US team sought to better understand the extent to which the Omicron variant is able to evade antibody neutralisation, by testing the activity of serum collected from a number of different patient samples. Initially the team created an Omicron pseudovirus and tested this against 10 sera samples collected from the Spring of 2020, which were likely to have been infected with the wild-type (original) COVID-19 virus. While there was a robust response to the wild-type, there was a greater than 32-fold reduction against Omicron and only two samples produced antibody titres above the limit of detection.

Vaccinated samples

The team then turned their attention to both fully vaccinated and third booster sera (TBS) samples. For the two mRNA-based vaccines, BNT162b2 and mRNA-1273, there was a >21-fold decrease in ID50 and > 8.6-fold decrease in boosted sera samples. For the other vaccines, Ad26.COV2.S and ChAdOx1, all samples produced antibody titres below the limit of detection apart from two samples for which the individual had a history of a prior infection.

Using 15 third booster sera samples obtained from BNT162b2 (13) and mRNA-1273, the researchers discovered that although each of these third booster sera produced antibody titres above the limit, there was a mean 6.5-fold drop compared to the wild-type.

Using authenticated Omicron isolates and samples from BNT162b2 and mRNA-1273, there was a greater than 6-fold drop in titres for fully vaccinated and a greater than 4.1-fold drop for boosted samples.

Finally, testing sera with monoclonal antibodies, the researchers found that all four combinations of monoclonal antibodies in clinical use lost substantial activity against Omicron.

Although this was a laboratory-based study and might not be replicated in clinical practice, the authors believed that COVID-19 is potentially only a mutation or two away from being resistant to current antibodies and that it was important to devise strategies that anticipate the evolutional direction of the virus and that future work should focus on the development of agents targeting conserved parts of the virus.

Citation

Liu L et al. Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2 BioRxiv 2021

Higher convalescent plasma antibody titre levels associated with lower risk of death in COVID-19

18th January 2021

Passive antibody transfer (convalescent plasma therapy) has been widely used to treat COVID-19; however, little is known about the effect on mortality of different antibody titre levels.

The use of convalescent plasma (CP) to treat respiratory infections has a long history having been used for over a century. During the current pandemic, interest in this therapeutic modality has picked up although the efficacy signals from this approach are still preliminary and require further study. As a result, a team led by researchers from the Department of Anaesthesiology and Peri-operative Medicine, Rochester, Minnesota, in the US, retrospectively studied the results obtained from an expanded-access programme to CP across a range of hospitals. Eligible patients were 18 years and over, hospitalised with a laboratory confirmed positive COVID-19 test and deemed at high risk for progression to severe or life-threatening COVID-19.

Treatment consisted of CP given intravenously although the corresponding IgG COVID-19 antibody levels within these samples were unknown. The researchers therefore collected and quantitively analysed, remnant aliquots of serum retained from the donation process for IgG antibody levels. These which were divided into low (<4.62), medium (4.62 to 18.45) and high (>18.45) titre levels. The primary outcome for the study was mortality at 30 days after transfusion of CP.

Findings
The patient cohort consisted of 3082 individuals of whom, 61% were male and 69% were younger than 70 years of age. In total, two-thirds received CP prior to mechanical ventilation. Death within 30 days after CP occurred in a 26.9% of all patients. Furthermore, the outcome occurred in 29.6%, 27.4% and 22.3% of those in the low, medium and high, IgG titre ranges respectively. The risk of death among those with higher antibody titre levels was reduced by 46% compared to the lowest antibody titre (relative risk, RR = 0.66, 95% CI 0.48-0.91) in patients who were not mechanically ventilated. However, there was no effect of antibody titre levels on death rates among patients who required mechanical ventilation.

The authors concluded that their data support the notion that the benefits of CP are largely dependent on the levels of antibody present within samples.

Citation
Joyner MJ et al. Convalescent plasma antibody levels and the risk of death from COVID-19. N Engl J Med 2021