Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

Cohen, Kristen W.; Linderman, Susanne L.; Moodie, Zoe; Czartoski, Julie; Lai, Lilin; Mantus, Grace; Norwood, Carson; Nyhoff, Lindsay E.; Edara, Venkata Viswanadh; Floyd, Katharine; Rosa, Stephen C. De; Ahmed, Hasan; Whaley, Rachael E.; Patel, Shivan; Prigmore, Brittany; Lemos, Maria P.; Davis, Carl W.; Furth, Sarah; O’Keefe, James B; Gharpure, Mohini P.; Gunisetty, Sivaram; Stephens, Kathy; Antia, Rustom; Zarnitsyna, Veronika I.; Stephens, David S.; Edupuganti, Srilatha; Rouphael, Nadine; Anderson, Evan J.; Mehta, Aneesh K; Wrammert, Jens; Suthar, Mehul S.; Ahmed, Rafi; McElrath, M. Juliana

doi:10.1016/j.xcrm.2021.100354

Cited by 363 publications

(405 citation statements)

References 45 publications

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“…Thus, measuring circulating antibody levels, their durability, specificity and recall kinetics is crucial for understanding and predicting the durability of protection (Cromer et al, 2021). As recently reported, among vaccinated HCW, the breakthrough infections were correlated with NAbT detected within the week immediately before (Bergwerk et al, 2021).The advantage of high NtAbs against the infection by viral variants was reported too (Cohen et al, 2021). Based on data reported here, a third mRNA vaccine dose is reasonable in uninfected subjects, to further boost immunity and recapitulate the effect observed in previously infected vaccinated subjects.…”

Section: Discussionmentioning

confidence: 89%

Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose

Vicenti

Basso

Gatti

et al. 2021

International Journal of Infectious Diseases

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Objectives : Our aim was to describe the longitudinal evolution of neutralizing antibody titres (NtAb) in three different cohorts of healthcare workers including vaccinated individuals with and without a previous SARS-CoV-2 infection and previously infected unvaccinated subjects. COVID-19 was mild or asymptomatic in those experiencing infection. Methods : NtAb was tested before BNT162b2 mRNA COVID-19 vaccine (V0), 20±2 days after the first dose (V1_20), 20±3 days (V2_20) and 90±2 days (V2_90) after the second dose in vaccinated HCW and after about 2 months (N_60), 10 months (N_300) and 13 months (N_390) from natural infection in unvaccinated HCW. NtAb was measured by authentic virus neutralization with a SARS-CoV-2 B.1 isolate circulating in Italy at HCW enrolment. Results : Sixty-two HCW were enrolled. NtAb were comparable in infected HCW with no or mild disease at all the study points. NtAb of uninfected HCW were significantly lower with respect to those of previously infected subjects at V1_20, V2_20 and V2_90. The median NtAb fold decrease from V2_20 to V2_90 was higher in the uninfected subjects with respect to subjects with mild infection (6.26 vs 2.58, p=0.03) and to asymptomatic HCW (6.26 vs 3.67, p=0.022). The median Nabt at N_390 was significantly lower with respect to N_60, p=0.007). Conclusions : In uninfected subjects completing the two-dose vaccine schedule, a third mRNA vaccine dose is a reasonable option to counteract the substantial NtAb decline occurring at a significantly higher rate compared to previously infected, vaccinated subjects. Although at low level Nabt are still at detectable level after 13 months in two third of previously infected and not vaccinated subjects.

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Section: Discussionmentioning

confidence: 89%

Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose

Vicenti

Basso

Gatti

et al. 2021

International Journal of Infectious Diseases

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“…In comparison, the half-life of live-virus neutralizing antibody response to mRNA1273 vaccination was 68 days (95% Cl: 61 to 75) as described in a previous study 10 . In contrast, the half-life of live-neutralizing antibody response was estimated as 150 days in COVID-19 infected individuals 11 . In the case of other inactivated vaccines such as the diphtheria or tetanus vaccines, the decay rates of the antibody response have been calculated to be in the order of a year or so 12 .…”

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confidence: 95%

Durability of immune responses to the BNT162b2 mRNA vaccine

Suthar

Arunachalam

et al. 2021

Preprint

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The development of the highly efficacious mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology. However, reports of waning vaccine efficacy, coupled with the emergence of variants of concern that are resistant to antibody neutralization, have raised concerns about the potential lack of durability of immunity to vaccination. We recently reported findings from a comprehensive analysis of innate and adaptive immune responses in 56 healthy volunteers who received two doses of the BNT162b2 vaccination. Here, we analyzed antibody responses to the homologous Wu strain as well as several variants of concern, including the emerging Mu (B.1.621) variant, and T cell responses in a subset of these volunteers at six months (day 210 post-primary vaccination) after the second dose. Our data demonstrate a substantial waning of antibody responses and T cell immunity to SARS-CoV-2 and its variants, at 6 months following the second immunization with the BNT162b2 vaccine. Notably, a significant proportion of vaccinees have neutralizing titers below the detection limit, and suggest a 3rd booster immunization might be warranted to enhance the antibody titers and T cell responses.

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“…After more than 300 days (up to 383 days) following infection among unvaccinated HCW, 90% were still seropositive for IgG against any of the S antigens, demonstrating persistence of immunity to natural exposure. This suggests maintenance of a certain level of protection irrespective of the additional role of memory T cell responses [52,54]. Based on our data, it is difficult to recommend how long previously exposed individuals could wait to get vaccinated, although receiving at least a dose of a mRNA vaccine if previously exposed clearly increases antibody levels and neutralizing capacity regardless of the time since infection.…”

Section: Discussionmentioning

confidence: 83%

“…Despite the clear impact of SARS-CoV-2 exposure on vaccines responses, time since infection did not have a major effect. In face of shortage of vaccine doses, and based on some studies reporting maintenance of antibody responses in COVID-19 recovered patients for more than 6 months [52][53][54][55] recommendations to wait up to 6-month post-infection to get vaccinated were issued in some countries, including Spain [23]. Nevertheless, at HCB, all HCW were recommended to get the vaccine although naïve individuals were prioritized.…”

Section: Discussionmentioning

confidence: 99%

Determinants of early antibody responses to COVID-19 mRNA vaccines in exposed and naive healthcare workers

Moncunill

Aguilar

Ribes

et al. 2021

Preprint

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Background Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naive adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. Methods We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects. A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with lower neutralization and antibody levels. Among fully vaccinated, 6.3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation Our data support administering a single-dose in pre-exposed healthy individuals. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year.

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Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

Cited by 363 publications

References 45 publications

Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose

Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose

Durability of immune responses to the BNT162b2 mRNA vaccine

Determinants of early antibody responses to COVID-19 mRNA vaccines in exposed and naive healthcare workers

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