Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine

Azzi, Lorenzo; Gasperina, Daniela Dalla; Veronesi, Giovanni; Shallak, Mariam; Maurino, Vittorio; Baj, Andreina; Gianfagna, Francesco; Cavallo, Pierpaolo; Dentali, Francesco; Tettamanti, L; Maggi, Fabrizio; Maffioli, Lorenzo; Tagliabue, Angelo; Accolla, Roberto S.; Forlani, Greta

doi:10.1016/j.ebiom.2022.104435

Cited by 23 publications

(32 citation statements)

References 51 publications

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“…Since SARS-CoV-2 infection became extremely prevalent in Europe and in the US, we speculate that some of the previous inconsistencies reported in the literature on saliva IgA responses might relate to difficulties recruiting participants who were truly SARS-CoV-2 naive. Many SARS-CoV-2 infections are indeed asymptomatic and even more so in the recent phases of virus circulation .…”

Section: Discussionmentioning

confidence: 91%

“…Several studies conclude that humoral mucosal immunity is largely driven by previous infection, with little impact of vaccination, 4 , 5 , 6 while others suggest that mRNA vaccination can by itself elicit long-lasting anti–SARS-CoV-2 mucosal IgA responses. 7 , 8 , 9 , 10 , 11 Herein, we compared individuals with previous SARS-CoV-2 infection and SARS-CoV-2–naive individuals included in the CoviCompare P and CoviCompare M vaccination trials 12 for their saliva and serum responses after 2 different modes of antigenic challenge: infection and vaccination or vaccination alone.…”

Section: Introductionmentioning

confidence: 99%

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Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

Gorochov,

Ropers,

Launay

et al. 2024

JAMA Netw Open

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ImportanceThere is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response.ObjectiveTo compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection.Design, Setting, and ParticipantsIn this cohort study, SARS-CoV-2–naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023.Main Outcomes and MeasuresAn ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times.ResultsA total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2–naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2–naive individuals. After vaccination, SARS-CoV-2–specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10−5 vs 37 × 10−5 at day 29; 107 × 10−5 vs 54 × 10−5 at day 57; and 104 × 10−5 vs 70 × 10−5 at day 180 [P &lt; .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2–naive group increased only at day 57 (36 × 10−5 vs 49 × 10−5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2–naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P &lt; .001).Conclusions and RelevanceThe findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

Gorochov,

Ropers,

Launay

et al. 2024

JAMA Netw Open

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“…Our results are consistent with the reported discrepancy between nAbs and COVID-19 vaccine VE in protection against death and severe disease (62). Although current COVID-19 mRNA vaccines administered by intramuscular route are poor in inducing mucosal immune responses (63)(64)(65), they can protect animals from SARS-CoV-2 infection of the upper respiratory tract, possibly due to the neutralizing IgG exudating from systemic circulation (22,42,64,65). Thus, nAbs may be more important in preventing SARS-CoV-2 infection of the upper respiratory tract than that of the lower respiratory tract.…”

Section: Discussionmentioning

confidence: 99%

A bivalent COVID-19 mRNA vaccine, PTX-COVID19-M1.2, elicited broad immune responses and protected animals from SARS-CoV-2 Omicron subvariants infection

liu,

Wang,

Kurtesi

et al. 2024

Preprint

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The continuous emergence of SARS-CoV-2 Omicron subvariants poses a serious threat thwarting the effectiveness of currently approved COVID-19 vaccines, demanding a vaccine that can provide broad protection against these subvariants. Although bivalent vaccines containing Omicron subvariant spikes have been shown to elicit high neutralizing antibodies (nAbs) and afford protection against homologous or antigenically close Omicron subvariants, the breadth and degree of the protection provided by the bivalent vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and efficacy of a bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) and Omicron BA.2.12.1, in mouse and hamster models. Both primary series and booster vaccination using M1.2 elicited potent and broad nAbs against Wuhan-Hu-1 (D614G) and Omicron subvariants, including BA.1, BA.2, BA.2.12.1, and BA.4/BA.5. Strong spike-specific T cell responses against Wuhan-Hu-1 and Omicron subvariants were also induced. In contrast, monovalent BA.2.12.1 spike-based mRNA vaccine elicited potent but narrower immune responses. Vaccination with M1.2 protected animals from Wuhan-Hu-1 and BA.1, BA.2, BA.5, and XBB.1.5 challenges. Interestingly, protection against XBB.1.5 lung infection did not correlate with nAb levels. These results indicate that M1.2 can generate a broadly protective immune response against multiple Omicron subvariants, including antigenically distant subvariants, and spike-specific T cells probably contribute to the breadth of the protection. Our findings have potential implications for designing COVID-19 booster vaccination strategies.

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“…As seen following third dose vaccination in our cohort [7] and elsewhere [20], protection from infection and protection by vaccination and infection (“hybrid immunity”) conferred longer-lasting immunity than vaccination alone. This may stem from the differential cellular immune responses to infection vs. vaccination [21], additionally, mucosal immunity appears to be conferred by infection rather than vaccination [22,23].…”

Section: Discussionmentioning

confidence: 99%

Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

Kirwan,

Hall,

Foulkes

et al. 2023

Preprint

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BackgroundThe protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers.MethodsParticipants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated.Results1,298 infections were detected among 9,560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95%CI 0.9 to 23.8) overall; 24.0% (95%CI 8.5 to 36.8) in the first two months post-vaccination, reducing to 10.3% (95%CI - 11.4 to 27.8) and 1.7% (95%CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95%CI 46.9 to 75.0) and 29.1% (95%CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection.ConclusionsDespite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern.FundingUK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, and others.

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Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine

Cited by 23 publications

References 51 publications

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

A bivalent COVID-19 mRNA vaccine, PTX-COVID19-M1.2, elicited broad immune responses and protected animals from SARS-CoV-2 Omicron subvariants infection

Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

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