Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years

Arbel, Ronen; Sergienko, Ruslan; Friger, Michael; Peretz, Alon; Beckenstein, Tanya; Yaron, Shlomit; Netzer, Doron; Hammerman, Ariel

doi:10.1038/s41591-022-01832-0

Cited by 125 publications

(122 citation statements)

References 22 publications

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“…Two dose AZD1222 has been showed to generate lower neutralisation titres and e cacy across different settings, in comparison to mRNA vaccines 2,3,28 . mRNA vaccine 'booster' third doses induce broader, potent responses against Omicron BA.1 2,29 and reduce mortality in the elderly 30 . Therefore, booster dosing after AZD1222 with mRNA vaccine should be considered in the African setting, even after natural infection and hybrid immunity, as future variants may be more pathogenic compared to BA.1 2,31,32 whilst maintaining immune evasion on a background of waning immunity.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa

Abdullahi

Oladele

Owusu

et al. 2022

Preprint

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There is a paucity of real-world data on vaccine elicited neutralising antibody responses for AZD1222, in African populations following vaccination scale up. Here, we first measured baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies coupled with pseudotyped virus neutralisation assays in two study cohorts from West Africa: Nigerian healthcare workers; (n = 140) and a Ghanaian general community cohort (n = 527). We found that 44% and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59% and 42% respectively with anti-receptor binding dominan (RBD) IgG specific antibodies. The increased prevalence of prior exposure using anti RBD antibodies was corroborated by Pseudotyped virus (PV) neutralizing antibody assays, indicating that overall, 50% of prior infections were missed by N antibody testing. PV titres (serum dilution required to inhibit 50% of infection, ID50) against wild type following 2-dose vaccination regimen were [145 (4.5) to 2579 (4.2) vs 57 (3.0) to 1049 (6.7)] (GMT ± s.d), delta [75 (3.0) to 549 (3.7) vs 37 (2.4) to 453 (7.4)] (GMT ± s.d) and omicron variants [37 (2.4) to 453 (7.4) vs 29 (1.8) to 95 (5.3)] (GMT ± s.d) in the Nigerian (1 month) vs Ghanaian participants (2 months) post vaccination (total n = 94). Previous IgG anti-N was associated with significantly higher neutralizing antibody levels with an observed 3.5-fold [1423 (3.9) vs 4674 (3.4)] (GMT ± s.d) and 2.7-fold [779 (7.1) vs 2128 (4.8) (GMT ± s.d) difference between N positive and negative participants in the Nigerian and Ghanaian cohorts respectively. We also observed serological evidence from N, S and RBD antibodies of breakthrough infection in 8/49 (16%) of Nigerian vaccinees over only 2 months, with neutralisation profiles suggesting delta variant infection consistent with the sampling period when this variant was known to dominate. Importantly, neutralising antibodies waned at 3 months after second dose vs 1 month post second-dose 1695 (4.3)] vs 2579 (4.2) in the Nigerian population who were N negative throughout. IgG anti-N was also observed to wane below cut-off in a total 19/94 (20%) of subjects highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent real world West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres at 6 months post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa

Abdullahi

Oladele

Owusu

et al. 2022

Preprint

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“…In summary, our updated findings suggest that waning effectiveness against hospital and emergency department admission after receiving a third dose of BNT162b2 vaccine is likely nuanced; that it is likely occurring for some high-risk individuals and in some settings (as was initially identified), but not in others. Despite emerging evidence from Israel showing that a fourth dose improves protection against severe outcomes, including hospitalisation and death, in the general older adult population, 5 , 6 , 7 more data are needed to fully understand long-term protection against omicron after a third dose and to inform recommendations for fourth doses (ie, second boosters) in those who are not high risk.…”

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confidence: 99%

Immunocompromise and durability of BNT162b2 vaccine against severe outcomes due to omicron and delta variants

Tartof¹,

Slezak²,

Puzniak³

et al. 2022

The Lancet Respiratory Medicine

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“…Furthermore, the decision on a second booster dose remains at present controversial. Three Israeli studies have examined the immunogenicity of a fourth mRNA booster dose; the first which enrolled 274 healthy healthcare workers reported a rather marginal benefit, as it offered a partial defense against the omicron variants [ 35 ], while the other two which included adults 60 years of age or older demonstrated a substantial reduction of confirmed SARS-CoV-2 infection cases (including severe illness) and hospitalizations or deaths due to COVID-19, respectively [ 36 , 37 ]. Apart from the lack of mature data with regard to the effectiveness of multiple booster shots, the EMA’s head of vaccines strategy, Mr. Marco Cavaleri, had recently raised concerns of T-cell exhaustion, thus weakening the immune responses, with frequent (i.e., every four months), additional doses [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Neutralizing Antibodies Kinetics Postvaccination in Cancer Patients under Treatment with Immune Checkpoint Inhibition

Terpos

Liontos

Fiste

et al. 2022

Cancers

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Considering that COVID-19 could adversely affect cancer patients, several countries have prioritized this highly susceptible population for vaccination. Thus, rapidly generating evidence on the efficacy of SARS-CoV-2 vaccination in the subset of patients with cancer under active therapy is of paramount importance. From this perspective, we launched the present prospective observational study to comprehensively address the longitudinal dynamics of immunogenicity of both messenger RNA (mRNA) and viral vector-based vaccines in 85 patients treated with immune checkpoint inhibitors (ICIs) for a broad range of solid tumors. Despite the relatively poor humoral responses following the priming vaccine inoculum, the seroconversion rates significantly increased after the second dose. Waning vaccine-based immunity was observed over the following six months, yet the administration of a third booster dose remarkably optimized antibody responses. Larger cohort studies providing real-world data with regard to vaccines effectiveness and durability of their protection among cancer patients receiving immunotherapy are an increasing priority.

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Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years

Cited by 125 publications

References 22 publications

SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa

SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa

Immunocompromise and durability of BNT162b2 vaccine against severe outcomes due to omicron and delta variants

SARS-CoV-2 Neutralizing Antibodies Kinetics Postvaccination in Cancer Patients under Treatment with Immune Checkpoint Inhibition

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