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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.

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

Booster COVID-19 vaccination improves immune response in cancer patients undergoing treatment

21st January 2022

A booster COVID-19 dose administered to cancer patients on active treatment leads to an improved immune response in those fully vaccinated

A booster COVID-19 dose to cancer patients with solid tumours in receipt of active treatment, improves their immune response, according to the results of a study by a team from the University Paris Est Créteil, Paris, France.

Since the start of the COVID-19 pandemic, cancer patients have been deemed to be at high risk and thus a priority group for access to available vaccines. Nevertheless, as cancer patients were excluded from the vaccine efficacy trials, the nature and level of the immunogenic response to vaccination among cancer patients was uncertain.

Data from a study among cancer patients on treatment has shown that after a first dose, 29% of patients were seropositive and that this rate increased to 86% after the second dose. But there appears to be only one study in patients with cancer who have received a third dose of vaccine and which appeared to show greater immunogenicity.

For the present study, the French team wanted to evaluate the immunogenicity of two and three doses of a COVID-19 vaccine in cancer patients currently receiving chemotherapy and how this was affected by the type of oncology treatment and the timing of vaccination.

Using a prospective, observational design, the team included patients with solid organ active cancer, which they defined as ‘histologic confirmation of solid cancer under treatment within the previous 6 weeks or starting treatment during the next 2 weeks.’

The researchers collected information on the patient’s cancer diagnosis, therapy and cancer stages. All patients had received two doses of BNT162b2 on days 0 and 21 and those who had a prior history of COVID-19 infection or evidence of antibodies before vaccination were excluded.

A booster COVID-19 (i.e., third) dose was offered to all of those who had a weak humoral response one month after the second dose, which was defined by an anti-spike protein antibody level below 1000 units.


In total, 163 patients with a median age of 66 years (53% male) were included in the analysis. The most common form of treatment was chemotherapy (75%), followed by targeted therapy (16%) and immunotherapy (9%).

One month after the first vaccine, only 15% of patients had anti-spike antibody titres > 1000, although one month after the second dose, this proportion increased to 65%. A booster COVID-19 dose was offered to 36 patients whose antibody level remained below 1000 units, one month after the second dose. This resulted in 75% of these patients, achieving antibody levels > 1000, one month after their third dose.

In their analysis, age, sex, cancer type, lymphopenia and use of corticosteroids four or more weeks before vaccination, were not associated with the level of immune response at the time of the second dose or even 28 days after the second dose.

However, patients receiving either chemotherapy or targeted therapy had a lower anti-spike level than those given immunotherapy (odds ratio, OR = 5.4, 95% CI 1.5 – 20.2, p = 0.02). Other factors such as the time between vaccination and intravenous chemotherapy administration were also not associated with the intensity of the humoral response.

The authors concluded that a booster COVID-19 dose among those with solid tumours and in receipt of treatment, improved the immune response, highlighting the importance of a third dose in this patient cohort.


Fenioux C et al. SARS-CoV-2 Antibody Response to 2 or 3 Doses of the BNT162b2 Vaccine in Patients Treated With Anticancer Agents JAMA Oncol 2022.