Promising booster vaccine with bivalent spike protein (Omicron BA.5/ancestral) for enhanced protection.
In a world grappling with the challenges posed by the emergence of various Omicron variants of the SARS-CoV-2 virus, the effectiveness of existing COVID-19 vaccines has been called into question due to the mutations present in the spike protein. As a response to this issue, scientists and researchers have been hard at work devising new strategies to update vaccines to effectively combat these new variants. Among these strategies are updated mRNA vaccines such as mRNA-1273.214 and CS-2034, as well as a recombinant protein vaccine known as V-01, all of which have shown promise in inducing a stronger immune response against Omicron variants compared to the original vaccines.
In a recent development, a team led by Chijioke Bennett has published the interim results of a phase 3 study in The Lancet Infectious Diseases. This study aimed to evaluate the safety and immunogenicity of a bivalent subunit vaccine (NVX-CoV2373 + NVX-CoV2540) containing spike proteins from both the ancestral strain and the Omicron BA.5 variant. This vaccine was given as a heterologous booster to adults who had previously received COVID-19 mRNA vaccines.
To assess the immunogenicity of the bivalent subunit vaccine, Bennett and colleagues measured IgG and neutralizing antibody levels against the ancestral strain, Omicron BA.5, and XBB.1.5. The results showed that the bivalent vaccine elicited significantly better neutralizing activity against Omicron BA.5 and XBB.1.5 compared to the prototype subunit vaccine (NVX-CoV2373) at day 28 after the booster doses. The study found that the geometric mean titre of anti-Omicron BA.5 neutralizing antibodies at day 28 after the second dose of the bivalent vaccine was 1017·8, with a 3·6-fold increase compared to the baseline level. In contrast, the prototype vaccine group showed a lower GMT of neutralizing antibodies against Omicron BA.5 at day 28, with a 1·8-fold increase from baseline. Interestingly, the monovalent BA.5 vaccinated group displayed the highest fold change of 4.4 from baseline. The study participants had previously received at least three doses of monovalent or bivalent mRNA vaccines, and the authors concluded that the heterologous boosting strategy with the bivalent subunit vaccine significantly enhanced pre-existing neutralizing activity induced by the mRNA vaccines.
Various COVID-19 vaccine platforms have been granted emergency approval, and studies have shown that heterologous prime-boost vaccination strategies generally lead to better immune responses compared to homologous approaches. For instance, in a phase 2 trial by Wu et al., an mRNA vaccine boosted anti-Omicron BA.5 neutralizing activity by 45·7-fold, while a homologous inactivated virus vaccine only boosted neutralizing antibodies by 2·9-fold. Similarly, superior immune responses were observed with combinations such as CoronaVac and BNT162b2 compared to homologous CoronaVac vaccination, and ChAdOx1-S and BNT162b2 compared to homologous ChAdOx1-S. Although a homologous subunit vaccine strategy was not directly evaluated in the study, the bivalent subunit vaccine as a heterologous booster significantly improved the humoral response in individuals previously primed with an mRNA vaccine.
Regarding safety, the bivalent subunit vaccine was well tolerated by participants in the study, with no withdrawals due to adverse events reported. While cellular responses were not specifically studied, the robust neutralizing antibody response against Omicron BA.5 and XBB.1·5 following two doses of the bivalent subunit vaccine suggests its effectiveness as a booster against Omicron variants. The study demonstrated that heterologous boosting in COVID-19 mRNA vaccine recipients was highly effective and is likely to be similarly effective in individuals previously primed with inactivated or adenovirus-vectored COVID-19 vaccines. This bivalent subunit vaccine presents a promising option as a booster for older adults and high-risk individuals, especially for those who may not be eligible for or prefer not to receive mRNA variant vaccines. The final report on the effectiveness and cellular responses of this bivalent subunit vaccine is eagerly anticipated. It is worth noting that the subunit protein vaccine has since been updated to a monovalent XBB.1.5 version.
In conclusion, the development of the bivalent (Omicron BA.5/ancestral) recombinant spike protein vaccine represents a significant step forward in the ongoing battle against COVID-19 and its rapidly evolving variants. By providing a potent immune response and demonstrating good tolerability, this vaccine holds promise as an effective booster for individuals previously vaccinated with mRNA vaccines. As the global effort to combat the pandemic continues, the findings from studies like
In a recent development, a team led by Chijioke Bennett has published the interim results of a phase 3 study in The Lancet Infectious Diseases. This study aimed to evaluate the safety and immunogenicity of a bivalent subunit vaccine (NVX-CoV2373 + NVX-CoV2540) containing spike proteins from both the ancestral strain and the Omicron BA.5 variant. This vaccine was given as a heterologous booster to adults who had previously received COVID-19 mRNA vaccines.
To assess the immunogenicity of the bivalent subunit vaccine, Bennett and colleagues measured IgG and neutralizing antibody levels against the ancestral strain, Omicron BA.5, and XBB.1.5. The results showed that the bivalent vaccine elicited significantly better neutralizing activity against Omicron BA.5 and XBB.1.5 compared to the prototype subunit vaccine (NVX-CoV2373) at day 28 after the booster doses. The study found that the geometric mean titre of anti-Omicron BA.5 neutralizing antibodies at day 28 after the second dose of the bivalent vaccine was 1017·8, with a 3·6-fold increase compared to the baseline level. In contrast, the prototype vaccine group showed a lower GMT of neutralizing antibodies against Omicron BA.5 at day 28, with a 1·8-fold increase from baseline. Interestingly, the monovalent BA.5 vaccinated group displayed the highest fold change of 4.4 from baseline. The study participants had previously received at least three doses of monovalent or bivalent mRNA vaccines, and the authors concluded that the heterologous boosting strategy with the bivalent subunit vaccine significantly enhanced pre-existing neutralizing activity induced by the mRNA vaccines.
Various COVID-19 vaccine platforms have been granted emergency approval, and studies have shown that heterologous prime-boost vaccination strategies generally lead to better immune responses compared to homologous approaches. For instance, in a phase 2 trial by Wu et al., an mRNA vaccine boosted anti-Omicron BA.5 neutralizing activity by 45·7-fold, while a homologous inactivated virus vaccine only boosted neutralizing antibodies by 2·9-fold. Similarly, superior immune responses were observed with combinations such as CoronaVac and BNT162b2 compared to homologous CoronaVac vaccination, and ChAdOx1-S and BNT162b2 compared to homologous ChAdOx1-S. Although a homologous subunit vaccine strategy was not directly evaluated in the study, the bivalent subunit vaccine as a heterologous booster significantly improved the humoral response in individuals previously primed with an mRNA vaccine.
Regarding safety, the bivalent subunit vaccine was well tolerated by participants in the study, with no withdrawals due to adverse events reported. While cellular responses were not specifically studied, the robust neutralizing antibody response against Omicron BA.5 and XBB.1·5 following two doses of the bivalent subunit vaccine suggests its effectiveness as a booster against Omicron variants. The study demonstrated that heterologous boosting in COVID-19 mRNA vaccine recipients was highly effective and is likely to be similarly effective in individuals previously primed with inactivated or adenovirus-vectored COVID-19 vaccines. This bivalent subunit vaccine presents a promising option as a booster for older adults and high-risk individuals, especially for those who may not be eligible for or prefer not to receive mRNA variant vaccines. The final report on the effectiveness and cellular responses of this bivalent subunit vaccine is eagerly anticipated. It is worth noting that the subunit protein vaccine has since been updated to a monovalent XBB.1.5 version.
In conclusion, the development of the bivalent (Omicron BA.5/ancestral) recombinant spike protein vaccine represents a significant step forward in the ongoing battle against COVID-19 and its rapidly evolving variants. By providing a potent immune response and demonstrating good tolerability, this vaccine holds promise as an effective booster for individuals previously vaccinated with mRNA vaccines. As the global effort to combat the pandemic continues, the findings from studies like
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