A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

Silva-Cayetano, Alyssa; Foster, William S.; Innocentin, Silvia; Belij‐Rammerstorfer, Sandra; Spencer, Alexandra J.; Burton, Oliver T.; Fra-Bidó, Sigrid; Lee, Jia Le; Thakur, Nazia; Conceicao, Carina; Wright, Daniel; Barrett, Jordan R.; Evans-Bailey, Nicola; Noble, Carly; Bailey, Dalan; Liston, Adrian; Gilbert, Sarah C.; Lambe, Teresa; Linterman, Michelle A.

doi:10.1016/j.medj.2020.12.006

Cited by 70 publications

(103 citation statements)

References 55 publications

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“…This IgG response showed mixed profile, with mainly IgG2 (IgG2a, IgG2b in both mouse strains and IgG2c in CD1 mice) and IgG1 subclasses (in both mouse strains) (Fig. 2A and B), which was similar to previously reported results after vaccination with ChAd alone 13 or saRNA alone 3 . Comparable amounts of SARS-CoV-2 spike-specific IgM were detected in all vaccinated groups (Fig.…”

Section: Resultssupporting

confidence: 91%

Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice

Spencer

McKay

Belij‐Rammerstorfer

et al. 2021

Preprint

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Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens, with high titre neutralising antibodies induced. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice.

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Section: Resultssupporting

confidence: 91%

Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice

Spencer

McKay

Belij‐Rammerstorfer

et al. 2021

Preprint

Self Cite

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“…As such it is not surprising that while a single dose of BNT162b2 failed to induce neutralizing antibodies in a proportion of participants, a second dose 3 weeks later resulted in all participants mounting a neutralizing antibody response. In aged mice the ChAdOx nCov-19 vaccine responses were reported as being lower as compared to younger mice, and this was overcome by booster dosing 17 . Importantly the UK REACT study, an observational community based study, has shown that the prevalence of IgG positivity was 34.7% 21 days after the first dose of BNT162b2 in those over 80 years 18 .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in the Moderna 1273 mRNA vaccine study in older individuals (above 55 years), neutralisation was only detectable after the second dose, whilst binding antibodies were detectable after both doses 9 . Interestingly, in aged mice the ChAdOx nCov-19 vaccine responses were lower as compared to younger mice, and this was overcome by booster dosing 10 .…”

Section: Discussionmentioning

confidence: 99%

Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2

Collier

Ferreira

Datir

et al. 2021

Preprint

116

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Vaccines remain the cornerstone for containing the SARS-CoV-2 pandemic. mRNA vaccines provide protection in clinical trials using a two-dose approach, separated by a three-week gap. Here we assessed real world immune responses following vaccination with mRNA-based vaccine BNT162b2. Following the first and second doses of the BNT162b2 vaccine, we measured IFNgamma; T cell responses, both total IgG Spike, IgG Spike RBD and neutralising antibody responses to Spike in sera using a lentiviral pseudotyping system. Median age was 82 amongst 26 participants. Three weeks after the first dose a lower proportion of participants over 80 years old achieved adequate neutralisation titre of >1:4 for 50% neutralisation as compared to those under 80 (8/15 versus 11/11, p<0.05). Mean neutralisation titres in this age group after the first dose were lower than in younger individuals (p<0.05). Following the second dose, neutralising antibody response 50% titres were above 1:4 in all individuals and there was no longer a difference by age grouping. A significant proportion of individuals over 80 appear to require a second dose of vaccine, given in this study at three weeks, to achieve virus neutralisation.

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“…Healthy ageing is associated with a change in the composition and function of the human immune system, and impaired antibody production upon vaccination (Henry et al, 2019; Carr et al, 2016; Liston et al, 2016; Allen et al, 2020; Stebegg et al, 2020; Nakaya et al, 2015). In aged mice, the defects in antibody production after vaccination can be attributed to a poor germinal center response, as the early extrafollicular plasmablast response is comparable in adult and aged mice (Silva-Cayetano et al, 2020). However, whether there are age-dependent defects in the GC response upon vaccination of older persons has not been directly demonstrated.…”

Section: Introductionmentioning

confidence: 99%

The memory B cell response to influenza vaccination is impaired in older persons

Carr

Wheatley

Hill

et al. 2021

Preprint

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Influenza imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how ageing impacts the memory B cell response we tracked haemagglutinin specific B cells by indexed flow sorting and single cell RNA sequencing in twenty healthy adults administered the trivalent influenza vaccine. We found age-related skewing in the memory B cell compartment six weeks after vaccination, with younger adults developing haemagglutinin specific memory B cells with an FCRL5+ 'atypical' phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We confirmed the germinal center ancestry of these FCRL5+ 'atypical' memory B cells using scRNASeq from fine needle aspirates of influenza responding human lymph nodes and paired blood samples. Together, this study shows that the aged human germinal center reaction and memory B cell response following vaccination is defective.

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A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

Cited by 70 publications

References 55 publications

Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice

Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice

Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2

The memory B cell response to influenza vaccination is impaired in older persons

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