DUBLIN – The Lancet Infectious Diseases has published the first clinical data on BBIBP-CorV, an inactivated whole virus vaccine directed against SARS-CoV-2. The early stage phase I/II study tested the Chinese-developed vaccine in 540 healthy volunteers, including 96 older participants. All vaccine recipients seroconverted and the adverse event profile was mild.

The phase I, dose-finding portion of the study recruited 192 volunteers, who were assigned to one of two age groups, ages 18 to 59 or 60 and older. Each received either placebo (n=24) or one of three regimens of the vaccine, comprising either 2 mcg (n=24), 4 mcg (n=24) or 8 mcg (n=24) administered on day zero (D0) and on D28.

All apart from the older vaccine recipients on the low-dose regimen seroconverted by D28 – seroconversion was defined as a minimum fourfold increase vs. baseline in levels of neutralizing antibody titers directed against the virus. Those in the older age group took longer than the younger vaccine recipients to seroconvert, and their neutralizing antibody titers were also lower. More than 75% of younger recipients seroconverted within 14 days of receiving the first dose, whereas older recipients who received either the medium or high doses attained a 100% seroconversion rate within 28 days; those in the low-dose group required 42 days to attain a 100% seroconversion rate.

The phase II part of the study examined the effects of differing dose schedules. Participants (n=448), who were all ages 18 to 59, received either placebo (n=112), a single 8-mcg dose of vaccine on D0 (n=84) or two 4-mcg shots of vaccine administered according to three different schedules (D0+D14, n=84; D0+D21, n=84; or D0+D28, n=84). Blinding was maintained by administering the placebo as required. Each of the two-dose schedules elicited a significantly higher D28 titer of neutralizing antibodies than the single-dose schedule of 8 mcg. The D0+D21 and D0+D28 schedules were also significantly more immunogenic than the D0+D14 schedule.

Whether the levels of neutralizing antibodies obtained will confer protection against circulating virus is an open question for now, given the lack of standardization of neutralizing antibody tests and the lack of field data – it is not clear what titers are required for protection against infection. According to the virus neutralizing assay used in the present study, the mean neutralizing titers were 282.7 for those on the D0+D21 schedule and 218 for those on the D0+D28 schedule.

During the phase I part of the study, 29% (42/144) of the participants who received the vaccine reported at least one adverse event within seven days, as compared with 17% (8/48) of placebo recipients. All were mild or moderate in severity, and no serious adverse events were recorded within the four-week period after vaccination. The most common systemic adverse event was fever, which was reported in 4% (4/144) of vaccine recipients and 6% (3/48) placebo recipients. Injection site pain and swelling, fatigue, gastrointestinal and mucocutaneous abnormalities were also reported but at a low incidence. The phase II part of the study yielded a similar picture – 23% (76/336) of vaccine recipients reported at least one adverse reaction but those were also mild or moderate in nature. The most common injection site reaction was pain, which occurred in 16% (53/336) of vaccine recipients and 4% (4/112) of placebo recipients. Two percent (7/336) of vaccine recipients experienced fever.

BBIBP-CorV, which is adjuvanted with aluminium hydroxide, is the second inactivated whole virus vaccine to be developed under the banner of the China National Biotec Group Co. Ltd., the biological products arm of the state-run China National Pharmaceutical Group Corp. (Sinopharm). Its Beijing Institute of Biological Products arm has taken the lead on this program. The vaccine was derived from a SARS-CoV-2 strain isolated from a hospitalized patient and was chosen on the basis of its high genetic stability and efficient replication in Vero cells, which are widely used for vaccine production. Preclinical studies demonstrated that, after multiple passages in Vero cells and beta-propiolactone inactivation, it could elicit high levels of neutralizing antibodies in nonhuman primates and several smaller animal species. It is currently undergoing two phase III trials.

In August, CNBG reported interim data from phase I/II studies of another inactivated SARS-CoV-2 vaccine, although that did not include older participants, who comprise a key constituency for vaccine developers given their risk profile. A third inactivated COVID-19 vaccine candidate, Coronavac, is in development at Beijing-based Sinovac Biotech Ltd., which recently gained approval to test the vaccine in a phase I/II trial in children and adolescents.

The present study, published on Oct. 15, was led by Wanshen Guo, of the Henan Provincial Center for Disease Control and Prevention, in Henan, and Xiaoming Yang, of Beijing Institute of Biological Products, in Beijing. BBIBP-CorV is currently undergoing a phase III trial in Abu Dhabi.

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