Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in saliva

Ketas, Thomas J.; Chaturbhuj, Devidas N.; Cruz-Portillo, Victor M; Francomano, Erik; Golden, Encouse B.; Chandrasekhar, Sharanya; Debnath, Gargi; Díaz-Tapia, Randy; Yasmeen, Anila; Leconet, Wilhem; Zhao, Zhen; Brouwer, Philip J.M.; Cushing, Melissa M.; Sanders, Rogier W.; Cupo, Albert; Klasse, Per Johan; Formenti, Silvia C.; Moore, John P.

doi:10.1101/2021.03.11.434841

Cited by 51 publications

(65 citation statements)

References 18 publications

(11 reference statements)

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“…In this study, only serum IgA was detected but multiple reports indicate that the amount of antigen-specific secretory IgA is correlated with serum levels in COVID-19 patients [ 14 , 15 ]. Anti-RBD IgA was also identified in the saliva and milk of vaccinated subjects, suggesting the induction of an efficient local immunity [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers

et al. 2021

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The BNT162b2 vaccine, containing lipid nanoparticles-formulated mRNA encoding the full-length spike protein of SARS-CoV-2, has been employed to immunize health care workers in Italy, administered in two doses 21 days apart. In this study, we characterized the antibody response induced by the BNT162b2 vaccine in a group of health care workers, tested at baseline, after the first dose and after the booster. Thirty-nine subjects without previous exposure to SARS-CoV-2 were vaccinated with the BNT162b2 vaccine. IgM, IgG, and IgA anti-receptor binding domain (RBD) were tested by ELISA. Neutralizing antibodies were evaluated testing the inhibition of RBD binding to ACE2. Antibody avidity was measured by urea avidity ELISA. IgM anti-RBD are produced after the first dose of vaccine and persist after the booster. IgG and IgA anti-RBD antibodies are detected in high amounts in all the subjects after the first dose and further increase after the booster. A few subjects, already after the first dose, produce antibodies inhibiting RBD interaction with ACE2. After the booster, high levels of inhibitory antibodies are detected in all the subjects. Affinity maturation takes place with boosting and IgG anti-RBD avidity increases with the number of immunizations. A less pronounced increase is observed with IgA. These data indicate that the BNT162b2 vaccine can induce high levels of protective antibodies of high avidity in vaccinated subjects; both IgG and IgA anti-RBD antibodies are produced. Further studies are needed to evaluate antibody persistence over time.

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Section: Discussionmentioning

confidence: 99%

BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers

et al. 2021

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“…Serum IgA levels are not a direct measure of secretory IgA levels, since systemic IgA are predominantly made of monomeric IgA1 subclass, and mucosal IgA is a polymeric IgA2 subclass 43 . However, induction of mucosal IgA after parenteral mRNA vaccination has been reported 41 . Our data shows that after full vaccination, spike IgA levels in serum correlated better to the levels of neutralizing antibodies in previously infected vaccine recipients than among naïve recipients, a phenomenon that may be related to a more mature immune response in the former group and recall of memory B cells from natural infection.…”

Section: Discussionmentioning

confidence: 99%

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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“…By quantifying the signal intensity on the test line (see Methods), we obtained an estimated antibody detection limit of ~ 0.30 µg mL -1 , ~ 50-fold lower than the total antibody concentration (~15 µg mL -1 ) in human saliva (Figure 2a) 33 .…”

Section: Performance Of the Nlf Assaymentioning

confidence: 99%

“…The concentration of IgG antibodies in human saliva is much lower (~15 µg mL -1 ) than in serum or blood (~15 mg mL -1 ), so antibodies against SARS-CoV-2 spike protein in saliva are more difficult to detect than in sera of COVID-19 infected individuals 11,24,27,33 . Several lab-based assays have been developed to meet this challenge, but not for saliva-based POC LF tests.…”

Section: A New Lateral Flow (Nlf) Assay Platformmentioning

confidence: 99%

A New Saliva-Based Lateral-Flow SARS-CoV-2 IgG Antibody Test for mRNA Vaccination

Shan¹,

Hsiung²,

Bliden

et al. 2021

Preprint

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Sensitive detection of IgG antibodies against SARS-CoV-2 is important to assessing immune responses to viral infection or vaccination and immunity duration. Antibody assays using non-invasive body fluids such as saliva could facilitate mass testing including young children, elderly and those who resist blood draws, and easily allowing longitudinal testing/monitoring of antibodies over time. Here, we developed a new lateral flow (nLF) assay that sensitively detects SARS-CoV-2 IgG antibodies in the saliva samples of vaccinated individuals and previous COVID-19 patients. The 25-minute nLF assay detected anti-spike protein (anti-S1) IgG in saliva samples with 100% specificity and high sensitivity from both vaccinated (99.51% for samples ≥ 19 days post 1st Pfizer/BioNTech or Moderna mRNA vaccine dose) and infected individuals. Antibodies against nucleocapsid protein (anti-NCP) was detected only in the saliva samples of COVID-19 patients and not in vaccinated samples, allowing facile differentiation of vaccination from infection. SARS-CoV-2 anti-S1 IgG antibody in saliva measured by nLF demonstrated similar evolution trends post vaccination to that in matching dried blood spot (DBS) samples measured by a quantitative pGOLD lab-test, enabling the nLF to be a valid tool for non-invasive personalized monitoring of SARS-CoV-2 antibody persistence. The new salivary rapid test platform can be applied for non-invasive detection of antibodies against infection and vaccination in a wide range of diseases.

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Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in saliva

Cited by 51 publications

References 18 publications

BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers

BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers

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 New Saliva-Based Lateral-Flow SARS-CoV-2 IgG Antibody Test for mRNA Vaccination

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