SARS-CoV-2 seropositivity after infection and antibody response to mRNA-based vaccination

Ciccone, Emily J.; Zhu, Deanna; Ajeen, Rawan; Lodge, Evans K; Shook-Sa, Bonnie; Boyce, Ross M.; Aiello, Allison E.

doi:10.1101/2021.02.09.21251319

Cited by 16 publications

(22 citation statements)

References 8 publications

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“…Consistent with several previous studies 7,8,21 , we found that in previously infected participants, a single dose of ChAdOx1 or BNT162b2 led to high anti-spike IgG antibody positivity and quantitative levels. Where vaccine supplies are limited, this supports prioritizing those without evidence of previous infection for vaccination and, in particular, delaying or omitting second doses in those with robust serological evidence of previous infection in these scenarios.…”

Section: Discussionsupporting

confidence: 92%

“…A study of 3,610 healthcare workers found that 99.5% and 97.1% seroconverted after a single dose of BNT162b2 or ChAdOx1, respectively, and that higher quantitative immunoglobulin G (IgG) levels were achieved in previously infected individuals 6 . Other studies have also found that single-dose BNT162b2 elicited higher antibody levels in previously seropositive individuals, levels that were comparable to those after two doses of vaccines in seronegative individuals [7][8][9] . Outside trials, there are limited data on post-vaccine antibody responses in other groups, especially older adults who were underrepresented in the ChAdOx1 trial 5 .…”

mentioning

confidence: 80%

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Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom

et al. 2021

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We report that in a cohort of 45,965 adults, who were receiving either the ChAdOx1 or the BNT162b2 SARS-CoV-2 vaccines, in those who had no prior infection with SARS-CoV-2, seroconversion rates and quantitative antibody levels after a single dose were lower in older individuals, especially in those aged >60 years. Two vaccine doses achieved high responses across all ages. Antibody levels increased more slowly and to lower levels with a single dose of ChAdOx1 compared with a single dose of BNT162b2, but waned following a single dose of BNT162b2 in older individuals. In descriptive latent class models, we identified four responder subgroups, including a ‘low responder’ group that more commonly consisted of people aged >75 years, males and individuals with long-term health conditions. Given our findings, we propose that available vaccines should be prioritized for those not previously infected and that second doses should be prioritized for individuals aged >60 years. Further data are needed to better understand the extent to which quantitative antibody responses are associated with vaccine-mediated protection.

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Section: Discussionsupporting

confidence: 92%

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confidence: 80%

Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom

et al. 2021

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“…A lack of increased spike binding antibody level after the second dose in those previously infected with SARS-CoV-2 has also been cited as evidence that the second dose is unnecessary 24,49,50 . Our data also shows a stable or declining antibody levels after the second dose in 2/3 rd of previously infected individuals (Figure 3A, group 2 or 3), a result that has also been noted by other 49,51,52 . Binding antibody levels after the first dose in the previously infected tend to increase by orders of magnitude; what our data shows is that in this group while after the second dose of vaccine higher antibody levels tend to decline, lower levels tend to increase, suggesting focusing of the immune response.…”

Section: Discussionsupporting

confidence: 88%

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

Narowski

Raphel

Adams

et al. 2021

Preprint

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With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naive and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naive and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naive people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.

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“…46, 47 A study of a cohort of health care workers recently published also confirmed that antibodies in seropositive individuals might boost the first dose. 48 This suggests that PCR confirmed seropositive individuals might potentially only require one dose of an mRNA vaccine, especially in cases where vaccine supplies are limited. 46,47 However, incorporating one dose of mRNA vaccine into a vaccine campaign may be a logistically complicated process.…”

Section: How Will Seropositive Individuals React After a Single Dose Of Vaccine?mentioning

confidence: 99%

“…Further research is required into the effect of prior infection to SARS-CoV-2 on the magnitude and durability of vaccination immune responses. 48…”

Section: How Will Seropositive Individuals React After a Single Dose Of Vaccine?mentioning

confidence: 99%

A review of leading COVID-19 vaccines, the quest for immune protection, and its key challenges. Part 3: Covid-19 vaccines – Key challenges and translational science

Hartshorne¹,

Villiers²

2021

Preprint

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Rationale• Developing and deploying safe and effective COVID-19 vaccines are faced with many challenges and unanswered questions.• Massive amounts of heterogenic scientific data are being generated that are needed rapidly to advance vaccine development, protect people and restore normality. • The purpose of Part 3 of this four-part series is to review the scientific considerations related to key challenges associated with COVID-19 vaccines and immune protection with the focus of making this data more meaningful and open for clinicians.Key points• The primary immunogen (antigen) required to induce neutralising antibodies (humoral) and T cell (cellular) immune responses is the S-protein fragment of SARS-CoV-2. • Currently, the evidence is firmly pointing towards neutralising antibodies, being more critical for protection.• Long-term protective or durable immune memory is driven by virus-specific T cell and B cell responses (adaptive immunity).• Circulating antibody titres are not predictive of T cell immune memory.• Durable immune memory is a crucial factor to sustain herd immunity.• Adjuvants are added to certain vaccines to provoke a more robust and durable immune response.• Adjuvants that provoke TH1-biased immune responses are preferred. • 90% of adults are seropositive for 'common cold' CoV strains.• There is a cross-reactivity between specific T cell of SARS-CoV-2 and 'common cold' CoV's.• Prior infection with 'common cold' can play a potentially protective role.• Seropositive individuals present with a rapid and higher antibody immune response after a single dose with an mRNA vaccine.• Vaccine-induced immune responses resulting in non-neutralising antibodies, low antibody titres, and abnormal T cell responses (TH2- biased) are potential risks for serious enhanced disease events but unlikely events.• Vaccine strategies aimed at inducing high titres on neutralising antibodies and TH1- biased immune responses reduce the risk of serious adverse events.• Emerging variants of concern are extremely infectious, highly transmissible and threatens the protective efficacy of current vaccines.Public health implications• A rapid global vaccination campaign combined with standard mitigation measures to stop transmission is the best defence against the emergence of further SARS-CoV-2 variants and the safest way to attain herd immunity.• Booster immunisations may be required to promote or improve the durability and strength of vaccine immunity.

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SARS-CoV-2 seropositivity after infection and antibody response to mRNA-based vaccination

Cited by 16 publications

References 8 publications

Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom

Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

A review of leading COVID-19 vaccines, the quest for immune protection, and its key challenges. Part 3: Covid-19 vaccines – Key challenges and translational science

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