WHF Position Statement on COVID Vaccination

Thienemann, Friedrich; Chakafana, Graham; Piñeiro, Daniel; Pinto, Fausto J.; Perel, Pablo; Singh, Kavita; Eiselé, Jean-Luc; Prabhakaran, Dorairaj; Sliwa, Karen

doi:10.5334/gh.1027

Cited by 1 publication

(1 citation statement)

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“…Over 15 different vaccines have been approved or authorized for emergency use worldwide, and the landscape is rapidly changing, with hundreds of candidates in various stages of clinical testing. [ 32 ] Not only are a wide variety of new vaccine technologies advancing through clinical trials, but clinical testing is also changing. Placebo controlled trials are becoming increasingly difficult to plan as populations become vaccinated and exposed to SARS‐CoV‐2, and thus some recent vaccine trials make use of an established comparator vaccine, with an endpoint of comparative neutralizing antibody titers.…”

Section: Introductionmentioning

confidence: 99%

Advanced Materials for SARS‐CoV‐2 Vaccines

et al. 2022

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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...

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Section: Introductionmentioning

confidence: 99%