Advanced Materials for SARS‐CoV‐2 Vaccines

Abstract

development, since it mediates viral entry and induces neutralizing antibody responses, which are predictive of protection from symptomatic SARS-CoV-2 infection. [2,3] As waves of new viral variants emerge, other targets such as the membrane (M), envelope (E), or nucleocapsid (N) proteins may emerge as complementary vaccine antigens to help increase breadth of protection. [4] S forms a homotrimeric structure comprising two domains, S1 and S2, separated by a Furin cleavage site (FCS). [5,6] S1 contains the receptor binding domain (RBD) which binds to human angiotensin converting enzyme 2 (hACE2) on host cells. Subsequently, proteolytic cleavage by Furin and by Transmembrane protease serine 2 (TMPRSS2) at the FCS and just upstream of the fusion peptide, respectively, activates the S2 fusion machinery leading to viral entry. [7] S is a class I fusion glycoprotein that undergoes major structural rearrangements from prefusion to post-fusion conformation during viral fusion to host cell membranes. It was previously shown that prefusion-stabilized class I fusion protein antigens better preserve neutralization epitopes for viruses including respiratory syncytial virus (RSV) fusion (F) glycoprotein. [8] Similar to the Middle East respiratory syndrome coronavirus (MERS-CoV) S protein, [9] two proline substitutions (2P) at residues 986 and 987 at the C-terminal boundary of the first heptad repeat were found to stabilize SARS-CoV-2 S in its prefusion conformation. [10] These 2P stabilizing mutations have been widely adopted in many SARS-CoV-2 vaccines including the Moderna mRNA-1273 vaccine (Spikevax), the Pfizer/BioNTech BNT162b2 vaccine (Comirnaty), the Novavax NVX-CoV2373 vaccine (Nuvaxovid), and the Johnson and Johnson Ad26.CoV2.S vaccine (Janssen COVID-19 Vaccine). [11] In contrast, the AstraZeneca/Oxford ChAdOx1 nCoV-19/AZD1222 (Vaxzevria) antigen uses the wildtype SARS-CoV-2 S sequence and cells transduced with the adenovirusvectored vaccine produce intact trimeric S, albeit with some proteolytic S degradation. [12] To mitigate this, another common antigen enhancement strategy used by NVX-CoV2373 [13] and Ad26.CoV2.S [14] for example, is to insert mutations or deletions at the proteolytic-prone FCS to improve antigen stability and preserve immunogenicity.As shown in the schematic illustration in Figure 1B, COVID-19 vaccines have taken on a wide variety of formats. Table 1 lists some of the vaccine types that have reported peerreviewed phase 3 clinical trial results so far. [16] Various advanced materials have emerged as vaccines for the S subunit antigen The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has killed untold millions worldwide and has hurtled vaccines into the spotlight as a go-to approach to mitigate it. Advances in virology, genomics, structural biology, and vaccine technologies have enabled a rapid and unprecedented rollout of COVID-19 vaccines, although much of the developing world remains unvaccinated. Several new vaccine platform...

Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins

“…Such agents could potentially not only maintain respiratory system function but also directly target a key step in infection. The design of vaccine adjuvants, which are often lipid-based, could also take advantage of the principles presented here to promote activity and stability (Mabrouk et al, 2022). Hence, the elucidation of how spike…”

A Diagnostic Strategy for Gauging Individual Humoral Ex Vivo Immune Responsiveness Following COVID-19 Vaccination

“…The rigidly scheduled regimen of re-vaccination currently employed to break the pandemic waves appears to be safe in terms of undesired side effects [ 22 ]. However, a more flexible vaccination strategy may have to be adopted eventually for the following reasons: (i) the duration of protection conveyed by current mRNA- and vector-based vaccines differs considerably [ 23 ]; (ii) the heterogeneity of duration of vaccination protection will further increase as protein- and whole-virus-based types of vaccines (such as Nuvaxovid (Novavax, Gaithersburg, MD, USA)) are introduced [ 24 ]; (iii) individual SARS-CoV-2 immunity and COVID-19 protection of vaccinated people is bound to vary even more due to unknown re-immunization by asymptomatic SARS-CoV-2-infections [ 25 , 26 ]; and (iv) ultimately, synchronous pandemic infection waves will lead to continuous asynchronous endemic re-infection, making it even more difficult to select optimal timepoints for re-vaccination [ 27 , 28 ].…”

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic that triggered an estimated 18 million deaths in 2020 and 2021 based on excess morality [ 1 ] and has re-emerged in waves of new variants [ 2 ]. In a remarkable display of the power of modern biotechnology, many safe, effective, and novel vaccines have effectively been rapidly developed and deployed [ 3 ]. As the human global population becomes exposed to COVID-19 viral infection and vaccines, the pandemic is expected to shift from pandemic to endemic, and many questions remain on how COVID-19 vaccines will be used in future years [ 4 ].…”