Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

Stolovich-Rain, Miri; Kumari, S; Friedman, Ahuva; Kirillov, Saveliy; Socol, Yakov; Billan, Maria; Pal, Ritesh Ranjan; Das, Kathakali; Golding, P R; Oiknine‐Djian, Esther; Sirhan, Salim; Sagie, Michal Bejerano; Cohen-Kfir, Einav; Gold, Naama; Fahoum, Jamal; Kumar, Manoj; Elgrably-Weiss, Maya; Zhou, Bing; Ravins, Miriam; Gatt, Yair E.; Bhattacharya, Saurabh; Zelig, Orly; Wiener, Reuven; Wolf, Dana; Elinav, Hila; Strahilevitz, Jacob; Padawer, Dan; Baraz, Lea; Rouvinski, Alexander

doi:10.3389/fimmu.2022.933347

Cited by 10 publications

(13 citation statements)

References 134 publications

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“…In this study, we observed that the titers of anti‐N‐specific IgG in the BAL samples of both groups showed stable and slightly upward trend at 6–10 weeks post prime immunization, although the levels in the N‐Ferritin group were significantly higher than those in the N group. Although the anti‐N‐specific IgA levels in the BAL samples of the N‐Ferritin group were higher, the IgA levels within the immune groups were much lower than those of the IgG, and these results were consistent with previous studies 39,40 . In summary, using nanoparticles as antigens can effectively improve the levels of anti‐N‐specific IgG and IgA in the lungs, which might be beneficial for reducing the probability of severe pneumonia.…”

Section: Disscussionsupporting

confidence: 90%

“…Although the anti-Nspecific IgA levels in the BAL samples of the N-Ferritin group were higher, the IgA levels within the immune groups were much lower than those of the IgG, and these results were consistent with previous studies. 39,40 In summary, using nanoparticles as antigens can effectively improve the levels of anti-N-specific IgG and IgA in the lungs, which might be beneficial for reducing the probability of severe pneumonia.…”

Section: Disscussionmentioning

confidence: 99%

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A conserved N protein nano‐vaccine of COVID‐19 exerts potent and cross‐reactive humoral and cellular immune responses in mice

Li,

Zhang,

Huang

et al. 2023

Journal of Medical Virology

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As severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) mutates continually, the current vaccines are unable to provide sufficient protection. It is important to develop a broad‐spectrum vaccine with conserved antigens to prevent variant infection. Here we fused the SARS‐CoV‐2 N protein with Helicobacter pylori nonheme ferritin to construct a SARS‐CoV‐2 N‐Ferritin nanoparticle vaccine. Compared with the monomer N protein, the N‐Ferritin nanoparticles induced more lymph node dendritic cells in mice to trigger adoptive immunity. Following this, the N‐Ferritin elicited more robust and long‐lasting antibody responses, which had better cross‐reactivity with the SARS‐CoV N protein. It is also worth noting that higher levels of N‐specific IgG and IgA were distributed in the lungs of N‐Ferritin‐immunized mice. Furthermore, the N‐Ferritin nanoparticles also resulted higher proportion of interferon‐γ+ CD8+ T cells, CD8+ Tcm cells, and T cells with cross‐reactivity in SARS‐CoV‐2, SARS‐CoV, and Middle East respiratory syndrome‐related coronavirus. The conserved N‐based nanoparticles could provide a promising vaccine developing strategy against SARS‐CoV‐2 variants and other coronaviruses.

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Section: Disscussionsupporting

confidence: 90%

Section: Disscussionmentioning

confidence: 99%

A conserved N protein nano‐vaccine of COVID‐19 exerts potent and cross‐reactive humoral and cellular immune responses in mice

Li,

Zhang,

Huang

et al. 2023

Journal of Medical Virology

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“…Importantly, we limited the study to individuals vaccinated at the beginning of the pandemic to select a substantial number of confirmed SARS-CoV-2-naive participants to be included in the study. 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 [3][4][5][6][7][8][9][10][11] 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: 99%

“…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%

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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“…While the systemic IgG response after vaccination has been studied in great detail, aspects of mucosal immunity after intramuscular vaccination against SARS-CoV-2 have been analyzed less extensively and yielded partially contradictory results. For example, BNT vaccine was reported to induce IgG and little or no specific IgA in the saliva with unclear neutralizing activity ( 14 ), while others reported the induction of both SARS-CoV-2-specific IgG and mucosal IgA after vaccination ( 15 – 18 ). Yet another study described systemic, but not mucosal SARS-CoV-2-specific Ig after vaccination ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Intramuscular vaccination against SARS-CoV-2 transiently induces neutralizing IgG rather than IgA in the saliva

Winklmeier,

Rübsamen,

Özdemir

et al. 2024

Front. Immunol.

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The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of mucosal immunity is less clear. Here, we analyzed kinetic and functional properties of anti-SARS-CoV-2 Abs in the saliva after vaccination with BNT162b2. We analyzed a total of 24 healthy donors longitudinally for up to 16 months. We found that specific IgG appeared in the saliva after the second vaccination, declined thereafter and reappeared after the third vaccination. Adjusting serum and saliva for the same IgG concentration revealed a strong correlation between the reactivity in these two compartments. Reactivity to VoCs correlated strongly as seen by ELISAs against RBD variants and by live-virus neutralizing assays against replication-competent viruses. For further functional analysis, we purified IgG and IgA from serum and saliva. In vaccinated donors we found neutralizing activity towards authentic virus in the IgG, but not in the IgA fraction of the saliva. In contrast, IgA with neutralizing activity appeared in the saliva only after breakthrough infection. In serum, we found neutralizing activity in both the IgA and IgG fractions. Together, we show that intramuscular mRNA vaccination transiently induces a mucosal immunity that is mediated by IgG and thus differs from the mucosal immunity after infection. Waning of specific mucosal IgG might be linked to susceptibility for breakthrough infection.

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Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

Cited by 10 publications

References 134 publications

A conserved N protein nano‐vaccine of COVID‐19 exerts potent and cross‐reactive humoral and cellular immune responses in mice

A conserved N protein nano‐vaccine of COVID‐19 exerts potent and cross‐reactive humoral and cellular immune responses in mice

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

Intramuscular vaccination against SARS-CoV-2 transiently induces neutralizing IgG rather than IgA in the saliva

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