Paucity and discordance of neutralising antibody responses to SARS-CoV-2 VOCs in vaccinated immunodeficient patients and health-care workers in the UK

Nadesalingam, Angalee; Cantoni, Diego; Wells, David A.; Aguinam, Ernest T; Ferrari, Matteo; Smith, Peter J. S.; Chan, Andrew; Carnell, George; Ohlendorf, Luis; Einhauser, Sebastian; George, Charlotte; Wagner, Ralf; Temperton, Nigel; Castillo‐Olivares, Javier; Baxendale, Helen; Heeney, Jonathan L.

doi:10.1016/s2666-5247(21)00157-9

Cited by 19 publications

(17 citation statements)

References 10 publications

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“…We also observed cross-neutralisation across VOCs in the vaccinated individuals. In agreement, studies done in the UK (Vaxzervria) and India (COVISHIELD) also show that a single dose of the AstraZeneca COVID-19 vaccine induces high antibody titres in individuals with previous SARS-CoV-2 exposure [ 13 , 27 ]. Of note, the UK study showed a significant increase in neutralising antibody titres to VOCs including alpha, beta, and gamma, but with the least increase observed for the beta and gamma variants [ 13 ].…”

Section: Discussionsupporting

confidence: 61%

“…Neutralising antibody titres induced following a single COVID-19 mRNA vaccine dose in previously infected individuals was 20-fold higher than after two doses of same vaccine in naïve individual. Moreover, these antibodies were shown to be cross-neutralising across multiple VOCs, including alpha and beta [ 10 , 13 – 15 ]. Recently, it has been shown that breakthrough infections in vaccinated individuals also demonstrate a hybrid immunity enhanced phenotype [ 16 , 17 ], observed in individuals vaccinated following prior SARS-CoV-2 infection [ 10 , 11 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2

Chibwana

Moyo-Gwete

Kwatra

et al. 2022

BMC Med

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Background Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. Methods Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Šídák's or Holm-Šídák's test. Results We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30–60 days vs. 210–270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. Conclusions These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2

Chibwana

Moyo-Gwete

Kwatra

et al. 2022

BMC Med

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“…In vitro neutralization assays of SARS-CoV-2 infectivity by patient plasma provide important evidence on the effectiveness of a humoral response against specific viral variants (47). Valid concerns have arisen that certain SARS-CoV-2 strains such as the Gamma and Delta variants may evolve the ability to at least partially evade natural and vaccine-initiated humoral immune responses (29,31). A study of 180 Finnish healthcare workers indicated that sera after 2-dose BNT162b2 vaccination effectively neutralized the D614G variant FIN-25 (identified in Spring 2020) representing the B.1 lineage and the Alpha variant (B.1.1.7; UK origin) but was only 20% as effective against the Beta variant (B.1.351, South Africa origin) (30).…”

Section: Discussionmentioning

confidence: 99%

“…It remains uncertain how long Covid-19 vaccination protection endures in different populations, and this knowledge becomes even more important with the emergence of new SARS-CoV-2 variants (29). Particular concern exists with the Beta variant (B.1351, South African origin) and the Delta variant (B.1.617.2, Indian origin), against which Covid-19 vaccination confers a measure of protection although reduced compared to previously detected SARS-CoV-2 strains such as the Alpha variant (B.1.1.7, UK origin) (30,31).…”

Section: Introductionmentioning

confidence: 99%

Anti-SARS-CoV-2 Immunoglobulin Isotypes, and Neutralization Activity Against Viral Variants, According to BNT162b2-Vaccination and Infection History

Tarkowski

Jager²,

Schiuma

et al. 2021

Front. Immunol.

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PurposeTo compare SARS-CoV-2 antigen-specific antibody production and plasma neutralizing capacity against B.1 wild-type-like strain, and Gamma/P.1 and Delta/B.1.617.2 variants-of-concern, in subjects with different Covid-19 disease and vaccination histories.MethodsAdult subjects were: 1) Unvaccinated/hospitalized for Covid-19; 2) Covid-19-recovered followed by one BNT162b2 vaccine dose; and 3) Covid-19-naïve/2-dose BNT162b2 vaccinated. Multiplex Luminex® immunoassays measured IgG, IgA, and IgM plasma levels against SARS-CoV-2 receptor-binding domain (RBD), spike-1 (S), and nucleocapsid proteins. Neutralizing activity was determined in Vero E6 cytopathic assays.ResultsMaximum anti-RBD IgG levels were similar in Covid-19‑recovered individuals 8‒10 days after single-dose vaccination and in Covid-19-naïve subjects 7 days after 2nd vaccine dosing; both groups had ≈2‑fold higher anti-RBD IgG levels than Unvaccinated/Covid-19 subjects tracked through 2 weeks post-symptom onset. Anti-S IgG expression patterns were similar to RBD within each group, but with lower signal strengths. Viral antigen-specific IgA and IgM levels were more variable than IgG patterns. Anti-nucleocapsid immunoglobulins were not detected in Covid-19-naïve subjects. Neutralizing activity against the B.1 strain, and Gamma/P.1 and Delta/B.1.617.2 variants, was highest in Covid‑19-recovered/single-dose vaccinated subjects; although neutralization against the Delta variant in this group was only 26% compared to B.1 neutralization, absolute anti-Delta titers suggested maintained protection. Neutralizing titers against the Gamma and Delta variants were 33‒77% and 26‒67%, respectively, versus neutralization against the B.1 strain (100%) in the three groups.ConclusionThese findings support SARS-CoV-2 mRNA vaccine usefulness regardless of Covid-19 history, and confirm remarkable protection provided by a single vaccine dose in people who have recovered from Covid-19.

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“…Nonetheless, in vitro neutralization studies and epidemiological vaccine efficacy studies indicate weaker protection against emerging variants for most of the non-mRNA vaccines. Moreover, regardless of the vaccine received, reductions in vaccine-elicited humoral immunity is likely to be clinically significant for persons with impaired immunity as a result of underlying disease, immunosuppressive drugs or older age [241][242][243][244] .…”

Section: Variants Of Interestmentioning

confidence: 99%

The biological and clinical significance of emerging SARS-CoV-2 variants

et al. 2021

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Among the many unprecedented aspects of the SARS-CoV-2 pandemic is the intense virological monitoring that has occurred, with more than two million virus isolates having undergone partial or complete genomic sequencing. Initially, genetic sequencing suggested that SARS-CoV-2 was exceptionally well adapted to humans, spreading rapidly with little evidence for natural selection among circulating viruses. This changed during the later months of 2020, with the first reports of emergent SARS-CoV-2 variants associated with increased transmissibility, disease severity and escape from humoral immunity.In this Review, we create a framework for understanding SARS-COV-2 variants by describing fundamental aspects of SARS-CoV-2 evolution, the structure and function of the SARS-CoV-2 spike protein and the laboratory methods used to characterize spike variants. We then describe the biological properties and epidemiological characteristics of these variants and their associated mutations. Lastly, we describe the types of study required for the research, clinical and public health communities to respond to the new threat posed by emerging SARS-CoV-2 variants. Given the wide public interest in this topic, we provide a box of key points. We also provide a repository of the SARS-CoV-2 variant neutralization data discussed in this Review (Stanford University Coronavirus Antiviral & Resistance Database -Susceptibility Data). SARS-CoV-2 evolutionCoronaviruses contain an exonuclease enzyme that reduces their replication error rate by about 15-fold to 20-fold in vitro, resulting in an in vivo viral mutation rate about 10-fold lower than that of influenza 1-3 . Nonetheless, they accumulate mutations and generate further diversity through the process of recombination when variants with different mutations infect the same host [4][5][6] . Recombination between different SARS-related coronaviruses is likely to have led to the emergence of SARS-CoV-2 (ref. 7 ) and, although it can be difficult to detect owing to the similarity of most sequences, recombination is occurring to some extent among circulating SARS-CoV-2 variants 6,8 . Additionally, host-mediated RNA editing by APOBeC and ADAr enzymes, as evidenced by the dominance of C to U changes in specific dinucleotide contexts, contributes to SARS-CoV-2 diversity 9,10 .Although it had been previously assumed that waning immunity explained the observation that people are commonly reinfected with endemic common-cold coronaviruses 11 , recent studies suggest that antigenic drift also contributes to the lack of long-lasting protection following coronavirus infections 12,13 . HCoV-229E and HCoV-OC43 sequences over a 30-year period demonstrate a ladder-like phylogenetic tree topology consistent with the emergence of novel variants sweeping

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Paucity and discordance of neutralising antibody responses to SARS-CoV-2 VOCs in vaccinated immunodeficient patients and health-care workers in the UK

Cited by 19 publications

References 10 publications

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2

Anti-SARS-CoV-2 Immunoglobulin Isotypes, and Neutralization Activity Against Viral Variants, According to BNT162b2-Vaccination and Infection History

The biological and clinical significance of emerging SARS-CoV-2 variants

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