Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

Comparison of the Effectiveness and Safety of Heterologous Booster Doses with Homologous Booster Doses for SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis

“…Among the 121 studies under full-text review, 98 studies were excluded. Eventually, 23 studies (including 13 published articles and 10 preprints) were included in this meta-analysis based on the inclusion criteria [ 14 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. The literature retrieval flow chart is shown in Figure 1 .…”

Long-term immune persistence induced by two-dose BBIBP-CorV vaccine with different intervals, and immunogenicity and safety of a homologous booster dose in high-risk occupational population. Secondary Study Based on a Randomized Clinical Trial

“…Recent studies reported the long-term immune persistence after the priming full-schedule vaccination and the safety and immunogenicity of booster dose with different technical platform COVID19 vaccines in different population [11][12][13][14][15][16][17][21][22][23].…”

“…Several studies reported that the homologous booster dose with inactivated vaccines led to a strangely rebound in neutralizing immune response against SARS-CoV-2. A non-peer-reviewed study [21] found the GMT of neutralizing antibodies was improved 1.04-3.87-fold on day 30 after a booster dose of BBIBP-CorV vaccine compared to the 28 days after the second dose. Similarly, one study [14] of 353 healthy adult participants who administered with a two-shot regiment (28 days apart) BBIBP-CorV vaccine (month 1) and a booster dose 7 months later, the GMT increased 4.5 times, compared to GMT of month 2.…”

“…Another non-peer-reviewed study [30] reported that a booster vaccination at 8 to 9 months after priming two-dose BBIBP-CorV vaccine led to a 6.1-fold increase in the neutralization GMT against the wild-type strain. Besides, some studies also revealed that a heterologous boost following prime vaccination could also elicit remarkably protection against SARS-CoV-2 [21, 23]. Consistent with previous studies, our research indicated that on 28 days after the homologous booster dose, GMT of neutralizing antibodies were increased by 8.91-12.16-fold compared to the pre-boosting levels and 1.98-2.50 fold compared to the 28 days after the second dose levels.…”

“…Besides, the fading immune response and the emergence of the Omicron (B.1.1.529) variant had raised concerns about the booster dose. Recent research revealed that a booster dose of different type of SARS-CoV-2 vaccine could induce remarkable high neutralizing antibody levels [21][22][23]. Nevertheless, the safety and immunogenicity of a booster dose with different priming two-dose BBIBP-CorV vaccination regimens are yet to be thoroughly evaluated, especially in the high-risk occupational population.…”