Statement on possible infections in SARS-CoV2 vaccinated persons and on the immunity of recovered persons

The rapid spread of new SARS-CoV-2 variants in England (B1.1.7 or variant of concern (VOC) 202012/01) and South Africa (B.1.351, also known as 501.V2 variant), which differ significantly from previously circulating variants in terms of their genome, raises the question of whether these variants are also widespread in Germany.

In variant B1.1.7, there are 8 mutations that lead to amino acid exchanges in the spike protein (S) of SARS-CoV-2, which possibly entail a change in the biological properties of S. One important amino acid exchange is found in the receptor binding motif[1] of S at position 501 (N501Y). This mutation, alone or in combination with other mutations, could lead to an increased binding ability to the human receptor ACE-2[2]. For another mutation, a deletion leading to the loss of amino acids at positions 69 and 70, an increase in the infectivity of the virus in cell cultures was shown in a previous publication[3].

Variant B.1.351, which was detected in South Africa, also contains 8 mutations that lead to amino acid exchanges in S of SARS-CoV-2. Two of these mutations are in the receptor binding motif (E484K and N501Y)[4]. Preliminary studies suggest that these mutations have very little effect on neutralisation by antibodies produced as a result of vaccination with an mRNA vaccine. However, these mutations appear to interfere with the binding of some antibodies being developed for therapy[5],[6].

The Coronavirus Consiliary Laboratory has currently analysed 1126 genome sequences of SARS-CoV-2 from all parts of Germany[7]. In the meantime, both variant B1.1.7 and variant B1.351 have been found. However, nothing can be said so far about the possible spread of these variants in Germany.

The sequencing of entire virus genomes and bioinformatic evaluation are time-consuming processes for which specific infrastructures are required, but which are not available everywhere. Therefore, current events are only inadequately recorded. An alternative is PCR methods for the targeted detection of the new SARS-CoV-2 variants, in order to be able to efficiently record the spread or spread of these variants by testing large numbers of samples. In addition, there are intensive efforts to improve the framework conditions for virus genome sequencing and thus molecular surveillance for SARS-CoV-2 in Germany.

According to a preliminary risk assessment by the European Centre for Disease Prevention and Control (ECDC), based on mathematical modelling[8], the new variant B1.1.7 may have a transmission rate up to 56% higher than previously circulating SARS-CoV-2 variants[9]. A study from the UK, which has not yet been peer-reviewed, also indicates a higher infection rate of SARS-CoV-2 variant B1.1.7[10]. However, this assessment must be verified in further studies. The GfV also points out that a more rapid spread of SARS-CoV-2 does not necessarily have to be accompanied by more severe courses of disease. However, it makes it clear once again that compliance with hygiene measures and contact reduction is urgently required. At the same time, the occurrence of virus variants shows that efforts for systematic molecular surveillance in Germany should be urgently intensified.

Mutations in SARS-CoV-2 can in principle have consequences for the efficacy of vaccines as well as for antibody therapy. An initial study has shown that sera from 20 participants in the previously published Phase 3 study of the BioNTech/Pfizer vaccine BNT162b2 (Comirnaty) neutralized a SARS-CoV-2 virus with a mutation at position 501 (a key mutation of the B1.1.7 variant) to the same extent as the virus without this mutation. So far, only very preliminary studies have been carried out on the possible effects of combinations of mutations such as those found in the above-mentioned variants. According to a publication that has not yet been peer-reviewed, the mutations in the B.1.351 variant from South Africa could significantly reduce the effectiveness of neutralizing antibodies in the serum of people who have previously been infected with the original SARS-CoV-2[11]. This could mean that these individuals are at risk of re-infection with the South African variant. In addition, this study provides preliminary evidence that these mutations reduce the efficacy of therapeutic S-specific antibodies, in some cases significantly. However, these observations must be assessed as preliminary and confirmed in further studies. However, they make the dynamics of SARS-CoV-2 and thus the need for rapid control of the pandemic very clear in order to minimize the risk of further variants emerging.
Conclusions:

- The vaccines used against SARS-CoV2 lead to protection against symptomatic or severe courses of the disease. For both vaccinated and recovered persons, there is a residual risk of asymptomatic infections and of the transmission of SARS-CoV2. Until more reliable data are available on the level of this risk, especially over time, the current hygiene measures (mandatory masks and distance rules) should also be maintained for vaccinated and recovered persons. This is especially true in areas with high incidence rates.

- Those who have recovered develop an immunological memory, and protection against new infections is well documented. When making a blanket equation between vaccinated and recovered individuals, the time courses of the protective immune response must be assessed both after vaccination and after infection. This must not be limited to the measurement of circulating antibodies, but must include the analysis of immunological memory as well as a priori planned monitoring of infections.

- We consider the recommendation of the STIKO to be sensible, according to which people who have recovered should also be vaccinated once against SARS-CoV2. This leads to a significant strengthening of immunity, which is particularly effective against VOC. In particular, older people who can only build up a weaker immune response due to immune senescence are then better protected.

- Long-term studies on the course of the immune response after vaccination and infection are necessary. This will allow the significance of VOC to be assessed and possible measures such as booster vaccinations to be evaluated.

The Board of Directors of the Society of Virology

Prof. Dr. Ralf Bartenschlager, Heidelberg University Hospital

Prof. Dr. Thomas Stamminger, University Hospital Ulm

Prof. Dr. Ulf Dittmer, University Hospital Essen

Prof. Dr. Sandra Ciesek, University Hospital Frankfurt

Prof. Dr. Klaus Überla, Erlangen University Hospital

With the participation of:

PD Dr. Sebastian Ulbert

Head of Department Vaccines and Infection Models

Fraunhofer Institute for Cell Therapy and Immunology

Perlickstr. 1, 04103 Leipzig

Sources

[1] Polack et al., DOI: 10.1056/NEJMoa2034577

[2] Voysey et al, https://doi.org/10.1016/S0140-6736(20)32661-1

[3] Dagan et al, DOI: 10.1056/NEJMoa2101765

[4] Vasileiou doi: 10.1016/S0140-6736(21)00677-2

[5] Hall et al, doi: 10.1016/S0140-6736(21)00790-X

[6] Haas E et al, https://doi.org/10.1016/S0140-6736(21)00947-8

[7] Amit S et al, doi: 10.1016/S0140-6736(21)00448-7

[8] Dan et al, doi: 10.1126/science.abf4063

[9] Rockstroh et al, doi: 10.1080/22221751.2021.1913973

[10] Gao et al, https://doi.org/10.1038/s41392-021-00525-3

[11] Sherina et al, doi: 10.1016/j.medj.2021.02.001

[12] Sokal et al,doi: 10.1016/j.cell.2021.01.050

[13] Reynolds et al, doi: 10.1126/science.abh1282 (2021)

[14] Stamatatos et al, doi 10.1126/science.abg9175 (2021)

[15] Hansen et al,doi: 10.1016/S0140-6736(21)00575-4