Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial

Kaabi, Nawal Al; Yang, Yun Kai; Zhang, Jing; Xu, Ke; Liang, Yu; Kang, Yubin; Su, Ji Guo; Yang, Tian; Hussein, Salah; ElDein, Mohamed Saif; Shao, Shuai; Yang, Sen; Lei, Wenwen; Gao, Xue; Jiang, Zhiwei; Wang, Hui; Li, Meng; Mekki, Hanadi Mekki; Zaher, Walid; Mahmoud, Sally; Zhang, Xue; Qu, Chang; Liu, Dan Ying; Yang, Mengjie; Eltantawy, Islam; Xiao, Peng; Wang, Zhao Nian; Yin, Jin Liang; Mao, Xiao Yan; Zhang, Jin; Liu, Ning; Shen, Fu Jie; Qu, Liang; Zhang, Yun Tao; Yang, Xiaoming; Wu, Guizhen; Li, Qi Ming

doi:10.1038/s41392-022-00984-2

Cited by 25 publications

(19 citation statements)

References 45 publications

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“…Preclinical animal studies showed that NVSI-06-09 elicited higher cross-neutralization to Omicron and other circulating variants than NVSI-06-07. 12 Comparing the results of this trial with the data from the trial on NVSI-06-07 reported previously, 11 the nAb levels boosted by NVSI-06-09 were remarkably higher than those by NVSI-06-07 against SARS-CoV-2 variants, especially Omicron. It should be mentioned that most of the participants in this trial had received three doses of BBIBP-CorV before booster vaccination, and those in the trial for NVSI-06-07 received two doses.…”

Section: Discussionsupporting

confidence: 56%

“…As an advanced vaccine developed based on NVSI-06-07, our first-generation trimeric RBD-based vaccine targeting the prototype SARS-CoV-2 virus, 10,11 NVSI-06-09 exhibited stronger immunogenic activities against the immune-evasive variants, including Omicron. Preclinical animal studies showed that NVSI-06-09 elicited higher cross-neutralization to Omicron and other circulating variants than NVSI-06-07.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies demonstrated that a booster dose of NVSI-06-07 following primary vaccination of the inactivated vaccine significantly improves the neutralizing antibody (nAb) responses against SARS-CoV-2. 10,11 NVSI-06-07 has been approved by the United Arab Emirates (UAE) for emergency use. The trimeric RBD that accommodates three RBDs in a single immunogen facilitates us to design a mosaic-type vaccine (NVSI-06-09), which integrates the key mutations from Omicron and other circulating variants into one molecule.…”

Section: Introductionmentioning

confidence: 99%

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Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

Kaabi

Yang²,

Liang

et al. 2022

Preprint

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BACKGROUND The rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODS An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTS A total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONS A booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

Kaabi

Yang²,

Liang

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Epitopes in less accessible regions of the RBD are more conserved among circulating coronaviruses, consistent with Abs targeting these regions being able to cross-neutralize other coronaviruses [21,25,26]. Several groups have developed adjuvanted RBD only vaccines based on monomeric or multivalent display of the RBD, with several human phase I/II and phase III trials showing a safe and immunogenic response, thus making the RBD, or S in the RBD-open state, an attractive vaccine antigen [27][28][29][30][31][32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 75%

“…The copyright holder for this preprint this version posted November 29, 2022. ; https://doi.org/10.1101/2022.11.29.518231 doi: bioRxiv preprint have developed adjuvanted RBD only vaccines based on monomeric or multivalent display of the RBD, with several human phase I/II and phase III trials showing a safe and immunogenic response, thus making the RBD, or S in the RBD-open state, an attractive vaccine antigen [27][28][29][30][31][32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Structural and Computational Design of a SARS-2 Spike Antigen with Increased Receptor Binding Domain Exposure and Improved Immunogenicity

Williams

Biancucci

Lessen

et al. 2022

Preprint

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Emerging SARS-CoV-2 variants of concern challenge the efficacy of approved vaccines and emphasize the need for improved antigens. Using an evolutionary-based design approach starting from the widely used engineered Spike antigen, S-2P, we sought to increase antigen production levels and the exposure of highly conserved and neutralization sensitive receptor-binding domain (RBD) epitopes. Thirty-six prototypes were generatedin silico, of which fifteen were produced and tested in biochemical assays. Design S2D14, which contains 20 mutations within the Spike S2 domain, showed a 6-fold increase in expression while preserving similar thermal stability and antigenicity as S-2P. Cryo-EM structures indicate that the dominant populations of S2D14 particles have RBDs in exposed states, and analysis of these structures revealed how modifications within the S2 domain balance trimer stability and RBD accessibility through formation and removal of hydrogen bonds and surface charge alterations. Importantly, vaccination of mice with adjuvanted S2D14 resulted in higher levels of neutralizing antibodies than adjuvanted S-2P against SARS-CoV-2 Wuhan strain and four variants of concern. These results can guide the design of next generation vaccines to combat current, and future coronaviruses and the approaches used may be broadly applicable to streamline the successful design of vaccine antigens.

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Effects of inactivated SARS‐CoV‐2 vaccination on male fertility: A retrospective cohort study

Dong

et al. 2022

Journal of Medical Virology

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Numerous studies have revealed severe damage to male fertility from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, raising concerns about the potential adverse impact on reproductive function of the coronavirus disease 2019 (COVID‐19) vaccine developed based on the virus. Interestingly, there are several researchers who have studied the impact of the COVID‐19 mRNA vaccine since then but have come up with conflicting results. As a near‐ideal candidate for mass immunization programs, inactivated SARS‐CoV‐2 vaccine has been widely used in many countries, particularly in less wealthy nations. However, little is known about its effect on male fertility. Here, we conducted a retrospective cohort study at a single large center for reproductive medicine in China between December 2021 and August 2022. Five hundred and nineteen fertile men with no history of laboratory‐confirmed COVID‐19 were included and categorized into four groups based on their vaccination status: unvaccinated group (n = 168), one‐dose vaccinated group (n = 8), fully vaccinated group (n = 183), and booster group (n = 160). All of them underwent a semen analysis and most had serum sex hormone levels tested. There were no significant differences in all semen parameters and sex hormone levels between the unvaccinated group and either vaccinated group. To account for possible vaccination‐to‐test interval‐specific changes, sub‐analyses were performed for two interval groups: ≤90 and >90 days. As expected, most of the semen parameters and sex hormone levels remained unchanged between the control and vaccinated groups. However, participants in vaccinated group (≤90 days) have decreased total sperm motility and increased follicle‐stimulating hormone level compared with the ones in unvaccinated group. Moreover, some trends similar to those found during COVID‐19 infection and recovery were observed in our study. Fortunately, all values are within the normal range. In addition, vaccinated participants reported few adverse reactions. No special medical intervention was required, and no serious adverse reactions happened. Our study suggests that inactivated SARS‐CoV‐2 vaccination does not impair male fertility, possibly due to the low frequency of adverse effects. This information reassures young male population who got this vaccine worldwide, and helps guide future vaccination efforts.

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Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial

Cited by 25 publications

References 45 publications

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

Structural and Computational Design of a SARS-2 Spike Antigen with Increased Receptor Binding Domain Exposure and Improved Immunogenicity

Effects of inactivated SARS‐CoV‐2 vaccination on male fertility: A retrospective cohort study

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