Differential durability of humoral and T cell immunity after two and three BNT162b2 vaccinations in adults aged &gt;80 years

Romero‐Olmedo, Addi J.; Schulz, Axel; Hochstätter, Svenja; Gupta, Dennis Das; Hirseland, Heike; Staudenraus, Daniel; Camara, Bärbel; Volland, Kirsten; Hefter, Véronique; Sapre, Siddhesh; Krähling, Verena; Müller-Kräuter, Helena; Mei, Henrik E.; Keller, Christian; Lohoff, Michael

doi:10.1101/2022.02.10.22270733

Cited by 3 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results clearly indicate that Gamma-or Delta-breakthrough sera with a high neutralizing activity against these VOCs are able to cross-neutralize Omicron BA.1, in agreement with previous studies [49,93,94,118], although our data only apply to vaccinated BTI infected with Delta and we cannot infer whether they extend to BTIs infected with other VOCs. Since breakthrough infection acts as a booster, this observation is congruent with the restoration of neutralizing ability induced by booster vaccination [27,28,44,46,48,57,[80][81][82][83][84][85][86][87][88]. It is currently acknowledged that vaccination of recovered COVID-19 patients with mRNA vaccines (hybrid immunity) induces IgG titers similar to or higher than two doses of vaccines in SARS-CoV-2-naïve individuals [36,101,119] and protects better against Omicron BA.1 than vaccination alone [48,49].…”

Section: Discussionmentioning

confidence: 74%

“…Accordingly, in vitro neutralization assays highlight a poor cross-neutralization of Omicron by sera from vaccinees [ 19 , 24 , 25 , 26 , 27 , 28 , 48 , 68 , 81 , 82 ]. Although booster vaccine doses restore neutralizing antibody (NAb) responses against Delta and partially against Omicron, they do not decrease viral load or transmission [ 27 , 28 , 44 , 46 , 48 , 57 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

Silva

Kohnen

Gilson

et al. 2022

IJMS

View full text Add to dashboard Cite

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

Silva

Kohnen

Gilson

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Our results clearly indicate that Gamma or Delta-breakthrough sera with high neutralizing activity against these VOCs are able to cross-neutralize Omicron BA.1, in agreement with previous studies [49,93,94,117], although our data apply to vaccinated BTI infected with Delta and we cannot infer whether they extend to BTIs infected with other VOCs. Since breakthrough infection acts as a booster, this observation is congruent with the restoration of neutralizing ability induced by booster vaccination [35,36,44,46,48,57,[81][82][83][84][85][86][87][88][89]. It is currently acknowledged that vaccination of recovered COVID-19 patients with mRNA vaccines (hybrid immunity) induces IgG titers similar to or higher than two doses of vaccines in SARS-CoV-2-naïve individuals [27,118,119] and protects better against Omicron BA.1 than vaccination alone [49].…”

Section: Discussionmentioning

confidence: 81%

“…Accordingly, in vitro neutralization assays highlight poor cross-neutralization of Omicron by sera from vaccinees [19, 32-36, 48, 68, 81, 82]. Although booster vaccine dose(s) restore neutralizing antibody (NAb) responses against Delta and partially against Omicron, they do not decrease viral load or transmission [35,36,44,46,48,57,[81][82][83][84][85][86][87][88][89][90].…”

Section: Introductionmentioning

confidence: 99%

Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

Silva

Kohnen

Gilson

et al. 2022

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here we compared the ability of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and from 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta to neutralize the ancestral B.1 strain, and the Gamma, Delta and Omicron BA.1 variants using live virus. We further determined antibody levels against the Spike protein, the Receptor Binding Domain (RBD) and the N-terminal domain (NTD) of Spike. Convalescent sera featured considerable variability in neutralization of B.1 and in cross-neutralization of different strains, and neutralizing capacity moderately correlated with antibody levels against Spike and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed higher neutralizing ability against all strains than patients with mild or severe forms of disease. Sera from BTI cases fell into one of two categories: half the sera had high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or very low neutralizing activity against all strains. Although antibody levels against Spike and the RBD were lower in BTI cases than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, indicative of cross-neutralization between B.1, Delta and Omicron and suggestive of higher affinity, as confirmed by the IC50:Ab level ratios. Neutralizing activity of BTI sera was strongly correlated with antibodies against Spike and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further suggest that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross neutralizing antibodies against different strains, including Omicron BA.1.

show abstract

“…These may suggest a ceiling effect on the T cell response among participants who previously received two doses of BNT162b2 and explain the lack of boost in cell-mediated immunity in the BB-C and BB-B arms, which has also been observed elsewhere. 28,31 Our study has several limitations. First, due to logistical challenges, we were only able to randomise at the time vaccination appointment was made but not at vaccination, and nearly half of randomized individuals dropped out before vaccination.…”

Section: Discussionmentioning

confidence: 94%

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

Leung

Cheng²,

Cohen

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac ("CC-C", n=101) or BNT162b2 ("CC-B", n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac ("BB-C", n=118) or BNT162b2 ("BB-B", n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Third doses significantly increased neutralising PRNT50 antibody titers against ancestral virus and Omicron BA.1 variant in all four study arms, and against Omicron BA.2 in all arms except CC-C, with statistically significant improvements for recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. Boosting of CD4+ T cells only occurred in CoronaVac-primed arms, but we did not identify overall differences between vaccine groups in CD4+ and CD8+ T cell responses. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

show abstract

Differential durability of humoral and T cell immunity after two and three BNT162b2 vaccinations in adults aged >80 years

Cited by 3 publications

References 11 publications

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

Contact Info

Product

Resources

About