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The 2019 coronavirus disease (COVID-19) pandemic has led to the unprecedented development of vaccines to help achieve herd immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without the death rates observed in many parts of the world.
Study: Use of eVLP-based vaccine candidates to enhance immunity against SARS-CoV-2 variants. Image Credit: Fit Ztudio / Shutterstock
As vaccines have been administered in millions of doses, initial hope has given way to a feeling of mistrust. This is largely due to the emergence of new variants capable of resisting the antibodies induced against the ancestral form of the virus, and therefore the vaccine antigen based on this wild strain.
Coronaviruses are large viruses with an RNA genome that replicates after entering the cell. Despite multiple replay mechanisms, mutations occur, many of which are deleterious and terminate the viral lineage. However, some are known to increase viral fitness and allow it to adapt better to the host.
As the virus continues to spread, other variations are inevitable. Some of them are called variants of concern (VOCs) because they are more transmissible, cause more severe disease, or may escape the immunity induced by earlier variants. Four established VOCs include the Alpha, Beta, Gamma, and Delta variants, all of which first spread locally to become dominant before crossing international borders.
The viral spike protein mediates attachment of the host cell via its receptor binding domain (RBD). It is a major target for escape mutations as well as for those which increase infectivity and virulence. All known VOCs have multiple common mutations on the spike protein, mainly in the RBD and the N-terminal domain (NTD).
VOC Alpha has the earlier D614G mutation linked to increased transmissibility but not immune evasion. The beta variant has both E484K and N501Y mutations in RBD which prevent its neutralization by antibodies induced by the ancestral strain, either by natural exposure or by vaccination.
The Delta variant has shown greater transmissibility than even the alpha lineage and the ability to break down immunity caused by vaccination, as evidenced by its rapid spread around the world, even in areas where high vaccine coverage has been achieved. It is characterized by the L452R mutation in RBD, shared by other variants such as Lambda, Kappa, Epsilon and Iota.
The P681R mutation in the furin cleavage site of the delta variant may also increase viral transmissibility.
The present study describes the performance of a candidate vaccine, VBI-2905a. This consists of enveloped viral-like particles (eVLP) which express a modified prefusion form of the beta spike protein and uses an adjuvant of aluminum phosphate (alum).
An earlier version of this vaccine, VBI-2902a, using the modified version of the ancestral tip, was found to have a strong neutralizing capacity in mice and hamsters protected against viral challenge with the ancestral SARS-CoV-2. . A phase I study showed quadruple or more neutralizing activity after two doses compared to COVID-19 recovery sera.
The researchers also examined another candidate, VBI-2901a, with an ancestral perfusion tip modified in addition to the SARS-CoV and MERS-CoV peak proteins.
A pre-printed version of the study is available on the website bioRxiv* server while the article is subject to peer review.
What did the study show?
The results of the study indicate a greater neutralizing efficacy in hamsters with VBI-2905a compared to the previous version, when the animal was exposed to the beta variant, as opposed to a homologous diet VBI-2902a.
A heterologous VBI-2902a prime-VBI-2905a booster regimen was found to induce neutralizing antibodies against ancestral, beta and delta variants.
With heterologous vaccination, the neutralizing activity against the ancestral strain was higher than with two doses of VBI-2905a, and was comparable to the levels achieved with homologous vaccination VBI-29052a. Against the Beta strain, the neutralizing titers reached levels similar to those obtained with a homologous diet VBI-2905a.
Antibody binding titers to RBD followed trends in neutralizing antibodies.
The trivalent vaccine candidate VBI-2901a produced neutralizing antibodies against the beta variant at higher titers than VBI-2902a and similar to VBI-2905a. It also neutralized pseudoviruses expressing both the peak Delta and Kappa variants, at titers three times higher than after using VBI-2902a. Thus, the absence of the peak beta antigen in the vaccine did not prevent a broad response of binding and neutralizing antibodies.
Conclusion
Further studies have shown that convalescent plasma from individuals recovered from previous SARS-CoV and who received Pfizer’s SARS-CoV-2 vaccine, containing the ancestral spike protein, contained largely neutralizing antibodies against ten Sarbecoviruses. The lineup included several variants of SARS-CoV-2, several variants of SARS-CoV, and the bat and pangolin coronaviruses.
Further studies will help determine the extent of broadly neutralizing activity with VBI-2901a, which produces equally broad exposure, protects against a wide range of coronaviruses and variants.
The study thus summarizes three alternatives for producing broad immunity against the ancestral, beta, delta and kappa variants of SARS-CoV-2 and related coronaviruses. Scientists say these results support their postulate that a vaccine containing several advanced proteins could trigger broad humoral immunity, thereby helping to neutralize new emerging variants of SARS-CoV-2 or even other coronaviruses.
*Important Notice
bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.
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