Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

Kustin, Talia; Harel, Noam; Finkel, Uriah; Perchik, Shay; Harari, Sheri; Tahor, Maayan; Caspi, Itamar; Levy, Rachel; Leschinsky, Michael; Dror, Shifra Ken; Bergerzon, Galit; Gadban, Hala; Gadban, Faten; Eliassian, Eti; Shimron, Orit; Saleh, Loulou; Ben‐Zvi, Haim; Amichay, Doron; Ben-Dor, Anat; Sagas, Dana; Strauss, Merav; Avni, Yonat Shemer; Huppert, Amit; Kepten, Eldad; Balicer, Ran D.; Nezer, Doron; Ben‐Shachar, Shay; Stern, Adi

doi:10.1101/2021.04.06.21254882

Cited by 109 publications

(94 citation statements)

References 23 publications

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“…[27][28][29] Pfizer/BioNTech has recently issued a press release reporting high efficacy in a study with a small number of recipients of the mRNA BNT162b2 vaccine conducted in the same population; however, a report from Israel suggests increased breakthrough infection rates by B.1.351 in BNT162b2 vaccinated individuals. 30,31 Studies have demonstrated reduced neutralization titers against the full B.1.351 variant following mRNA-1273 vaccination, although levels are still significant and expected to be protective based on challenge studies in NHPs. 30,31 Despite this prediction of continued efficacy of mRNA-1273 against this key variant of concern (VOC), the magnitude and duration of vaccine mediated protection is still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…30,31 Studies have demonstrated reduced neutralization titers against the full B.1.351 variant following mRNA-1273 vaccination, although levels are still significant and expected to be protective based on challenge studies in NHPs. 30,31 Despite this prediction of continued efficacy of mRNA-1273 against this key variant of concern (VOC), the magnitude and duration of vaccine mediated protection is still unknown. Moreover, a key related question is whether development of new mRNA vaccines to match the B.1.351 variant will enable enhanced neutralization responses and durability.…”

Section: Introductionmentioning

confidence: 99%

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Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Choi

Koch

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna's COVID-19 vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Choi

Koch

et al. 2021

Preprint

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“…In (Jackson et al, 2020), we could read : «Last, codon optimization and modification of nucleotides have contributed to translation efficiency. For example, optimization of guanine and cytosine (GC) content can have a significant impact (Kudla et al, 2016) and has been well established with DNA vaccines ». (Kudla et al, 2016) detailed this « CG rich manufacturing technology » : « Mammalian genes are highly heterogeneous with respect to their nucleotide composition, but the functional consequences of this heterogeneity are not clear.…”

Section: 00481884mentioning

confidence: 99%

“…For example, optimization of guanine and cytosine (GC) content can have a significant impact (Kudla et al, 2016) and has been well established with DNA vaccines ». (Kudla et al, 2016) detailed this « CG rich manufacturing technology » : « Mammalian genes are highly heterogeneous with respect to their nucleotide composition, but the functional consequences of this heterogeneity are not clear. In the previous studies, weak positive or negative correlations have been found between the silent-site guanine and cytosine (GC) content and expression of mammalian genes.…”

Section: 00481884mentioning

confidence: 99%

SARS-CoV2 Variants and Vaccines mRNA Spikes Fibonacci Numerical UA/CG Metastructures

Pérez¹

2021

Preprint

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In this paper, we suggest a biomathematical numerical method analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions. This method is used to evaluate then compare the spike genes related to the main SARS-CoV2 VARIANTS circulating presently within the world. The 9 main results proposed to be reproduced by peers are: 1/ SARS-CoV2 genome and spike evolution in one year 2020-2021. 2/ SARS-CoV2 Origins. 3/ Comparing 11 reference variants spikes. 4/ analysing 32 CAL.20C california variant patients spikes. 5/ Toward a meta mRNA Fibonacci gene end message code. 6/ analysing S501 UK, S484 South Afrika and « 2 mutations » IINDIA variants. 7/ Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectuosity. 8/ Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA. 9/ Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies? Particularly, we suggest the following conjecture at mRNA folding level : CONJECTURE of SARS-CoV2 VARIANTS: The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Afrika, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA. Finally, we show that this kind of Fibonacci matastructures disapears TOTALLY analysing the published mRNA sequences of PFIZER and MODERNA vaccines. One fact is certain, the 2 mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine because by doping these sequences in CG rich, their designers, in search of greater STABILITY of these RNAs will have built, according to us , sequences which, as soon as they are inserted into the human host, will seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve, paradoxically, their STABILITY and probably also their LIFETIME.. Particularly, using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the 2 vaccines Moderna and Phizer, we conclude a very probable difference in stability and shelf life of the 2 respective mRNAs of these 2 vaccines. However, the “State of the Art” will tell you that their 2 protein sequences are strictly identical. However, by having modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the 2 cases. We can only note the great ADAPTATION power - at the global scale of their genomes - of the most infectious VARIANTS such as the BRAZIL 20J / 501Y.V3 variant (P.1). This is very worrying for the VACCINES <==> VARIANTS run: We demonstrate how the Brazilian variant P.1 which becomes uncontrollable in Brazil in April 2021 has a level of organization of long metastructures of 17,711 bases covering the genome which is 3.6 more important than that of the 2 reference genomes SARS-CoV2 Wuhan and worldwide D614G. We suggest that this high level of overall structure of this variant contributes to the stability of this genome and, possibly, to its greater contagiousness.

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“…10 The Pfizer/BioNTech BNT162b2 mRNA vaccine was reported to be less effective against B.1.351 than against non-B.1.351 variants based on a small analysis of breakthrough infections that were enriched for B.1.351 in Israel. 11 The efficacy of CoronaVac/Sinovac inactivated virus vaccine in Brazil, where 75% of infections were with the P.1 variant, was estimated at around 50% against symptomatic infection. 12…”

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confidence: 99%

SARS-CoV-2 vaccines and their challenges against the variants

Shrestha¹

2021

J Adv Intern Med

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The coronavirus disease 2019 (COVID-19) pandemic has lead to the several researches for the development of the new severe acute respiratory syndrome corona virus 2 (SARSCoV- 2) vaccines, namely mRNA vaccine, viral vector vaccine, recombinant protein vaccine and inactivated vaccine, with an objective to achieve the response which include production of neutralizing antibodies, generation of a T-cell response, and avoidance of immune-enhanced disease. Over a course of time, the SARS-CoV-2 virus has evolved and lead to mutations; the virus with one or more new mutations is referred to as a “variant” of the original virus. All new strains (P.1 from Brazil, B.1.351 from South Africa, B.1.1.7 from the UK and B.1.617 from India) have mutations in the spike protein, resulting in the threat to the effectiveness of the current available first generation vaccines. Hence, there might be the need of the development of the modified next generation of vaccines, which take care of all those variants. Nevertheless, the current first generation vaccines may still provide satisfying immunity against SARS-CoV-2 variants. Most vaccines are expected to provide protection against hospitalizations/deaths from these variants and a booster vaccine against these variants is likely to be effective. Hence, the current vaccination must proceed. As we are aware that the more the virus spreads, the more variants are likely to appear. In order to stop the spread of SARS-CoV-2 variants, it is important to get the vaccines once it is available and not to forget about the need to wash hands frequently, keep at least 1m distance from others and wear a mask. With the development of the effective SARS-CoV-2 vaccines and implementation of public health measures, we can surely defeat SARS-CoV-2 virus in COVID-19 battle and end this pandemic.

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Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

Cited by 109 publications

References 23 publications

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

SARS-CoV2 Variants and Vaccines mRNA Spikes Fibonacci Numerical UA/CG Metastructures

SARS-CoV-2 vaccines and their challenges against the variants

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