Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva
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Abstract
The approved Pfizer and Moderna mRNA vaccines are well known to induce serum antibody responses to the SARS-CoV-2 Spike (S)-protein. However, their abilities to elicit mucosal immune responses have not been reported. Saliva antibodies represent mucosal responses that may be relevant to how mRNA vaccines prevent oral and nasal SARS-CoV-2 transmission. Here, we describe the outcome of a cross-sectional study on a healthcare worker cohort (WELCOME-NYPH), in which we assessed whether IgM, IgG, and IgA antibodies to the S-protein and its receptor-binding domain (RBD) were present in serum and saliva samples. Anti-S-protein IgG was detected in 14/31 and 66/66 of saliva samples from uninfected participants after vaccine doses-1 and -2, respectively. IgA antibodies to the S-protein were present in 40/66 saliva samples after dose 2. Anti-S-protein IgG was present in every serum sample from recipients of 2 vaccine doses. Vaccine-induced antibodies against the RBD were also frequently present in saliva and sera. These findings may help our understanding of whether and how vaccines may impede SARS-CoV-2 transmission, including to oral cavity target cells.
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References
Klasse PJ, Nixon DF, Moore JP. Immunogenicity of clinically relevant SARS-CoV-2 vaccines in nonhuman primates and humans. Sci Adv. 2021;7(12). doi: 10.1126/sciadv.abe8065. PubMed PMID: 33608249; PMCID: PMC7978427.
Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586(7830):516-27. doi: 10.1038/s41586-020-2798-3. PubMed PMID: 32967006.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T, Group CS. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-16. doi: 10.1056/NEJMoa2035389. PubMed PMID: 33378609; PMCID: PMC7787219.
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW, Jr., Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC, Group CCT. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-15. doi: 10.1056/NEJMoa2034577. PubMed PMID: 33301246; PMCID: PMC7745181.
Huang N, Perez P, Kato T, Mikami Y, Okuda K, Gilmore RC, Conde CD, Gasmi B, Stein S, Beach M, Pelayo E, Maldonado JO, Lafont BA, Jang SI, Nasir N, Padilla RJ, Murrah VA, Maile R, Lovell W, Wallet SM, Bowman NM, Meinig SL, Wolfgang MC, Choudhury SN, Novotny M, Aevermann BD, Scheuermann RH, Cannon G, Anderson CW, Lee RE, Marchesan JT, Bush M, Freire M, Kimple AJ, Herr DL, Rabin J, Grazioli A, Das S, French BN, Pranzatelli T, Chiorini JA, Kleiner DE, Pittaluga S, Hewitt SM, Burbelo PD, Chertow D, Consortium NC-A, Oral HCA, Craniofacial Biological N, Frank K, Lee J, Boucher RC, Teichmann SA, Warner BM, Byrd KM. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med. 2021;27(5):892-903. doi: 10.1038/s41591-021-01296-8. PubMed PMID: 33767405.
Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B, Wang JH, Li Z, Chao G, Rojas OL, Bang YM, Pu A, Christie-Holmes N, Gervais C, Ceccarelli D, Samavarchi-Tehrani P, Guvenc F, Budylowski P, Li A, Paterson A, Yue FY, Marin LM, Caldwell L, Wrana JL, Colwill K, Sicheri F, Mubareka S, Gray-Owen SD, Drews SJ, Siqueira WL, Barrios-Rodiles M, Ostrowski M, Rini JM, Durocher Y, McGeer AJ, Gommerman JL, Gingras AC. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020;5(52). doi: 10.1126/sciimmunol.abe5511. PubMed PMID: 33033173; PMCID: PMC8050884.
Russell MW, Moldoveanu Z, Ogra PL, Mestecky J. Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Front Immunol. 2020;11:611337. doi: 10.3389/fimmu.2020.611337. PubMed PMID: 33329607; PMCID: PMC7733922.
Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184(4):861-80. doi: 10.1016/j.cell.2021.01.007. PubMed PMID: 33497610; PMCID: PMC7803150
Corbett KS, Nason MC, Flach B, Gagne M, S OC, Johnston TS, Shah SN, Edara VV, Floyd K, Lai L, McDanal C, Francica JR, Flynn B, Wu K, Choi A, Koch M, Abiona OM, Werner AP, Alvarado GS, Andrew SF, Donaldson MM, Fintzi J, Flebbe DR, Lamb E, Noe AT, Nurmukhambetova ST, Provost SJ, Cook A, Dodson A, Faudree A, Greenhouse J, Kar S, Pessaint L, Porto M, Steingrebe K, Valentin D, Zouantcha S, Bock KW, Minai M, Nagata BM, Moliva JI, van de Wetering R, Boyoglu-Barnum S, Leung K, Shi W, Yang ES, Zhang Y, Todd JM, Wang L, Andersen H, Foulds KE, Edwards DK, Mascola JR, Moore IN, Lewis MG, Carfi A, Montefiori D, Suthar MS, McDermott A, Sullivan NJ, Roederer M, Douek DC, Graham BS, Seder RA. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates. bioRxiv. 2021; doi: 10.1101/2021.04.20.440647. PubMed PMID: 33907752; PMCID: PMC8077626.
Francica JR, Flynn BJ, Foulds KE, Noe AT, Werner AP, Moore IN, Gagne M, Johnston TS, Tucker C, Davis RL, Flach B, O'Connell S, Andrew SF, Lamb E, Flebbe DR, Nurmukhambetova ST, Donaldson MM, Todd JM, Zhu AL, Atyeo C, Fischinger S, Gorman MJ, Shin S, Edara VV, Floyd K, Lai L, Tylor A, McCarthy E, Lecouturier V, Ruiz S, Berry C, Tibbitts T, Andersen H, Cook A, Dodson A, Pessaint L, Ry AV, Koutsoukos M, Gutzeit C, Teng IT, Zhou T, Li D, Haynes BF, Kwong PD, McDermott A, Lewis MG, Fu TM, Chicz R, van der Most R, Corbett KS, Suthar MS, Alter G, Roederer M, Sullivan NJ, Douek DC, Graham BS, Casimiro D, Seder RA. Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates. bioRxiv. 2021; doi: 10.1101/2021.03.02.433390. PubMed PMID: 33688652; PMCID: PMC7941623.
Froberg J, Diavatopoulos DA. Mucosal immunity to severe acute respiratory syndrome coronavirus 2 infection. Curr Opin Infect Dis. 2021;34(3):181-6. doi: 10.1097/QCO.0000000000000724. PubMed PMID: 33899752.
Martinez-Valdebenito C, Andaur C, Angulo J, Henriquez C, Ferres M, Le Corre N. Characterization of Oral Immunity in Cases and Close Household Contacts Exposed to Andes Orthohantavirus (ANDV). Front Cell Infect Microbiol. 2020;10:557273. doi: 10.3389/fcimb.2020.557273. PubMed PMID: 33224896; PMCID: PMC7670062.
Matsuda K, Migueles SA, Huang J, Bolkhovitinov L, Stuccio S, Griesman T, Pullano AA, Kang BH, Ishida E, Zimmerman M, Kashyap N, Martins KM, Stadlbauer D, Pederson J, Patamawenu A, Wright N, Shofner T, Evans S, Liang CJ, Candia J, Biancotto A, Fantoni G, Poole A, Smith J, Alexander J, Gurwith M, Krammer F, Connors M. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity. J Clin Invest. 2021;131(5). doi: 10.1172/JCI140794. PubMed PMID: 33529172; PMCID: PMC7919717.
Salisch NC, Izquierdo Gil A, Czapska-Casey DN, Vorthoren L, Serroyen J, Tolboom J, Saeland E, Schuitemaker H, Zahn RC. Adenovectors encoding RSV-F protein induce durable and mucosal immunity in macaques after two intramuscular administrations. NPJ Vaccines. 2019;4:54. doi: 10.1038/s41541-019-0150-4. PubMed PMID: 31885877; PMCID: PMC6925274.
Patterson EI, Prince T, Anderson ER, Casas-Sanchez A, Smith SL, Cansado-Utrilla C, Solomon T, Griffiths MJ, Acosta-Serrano A, Turtle L, Hughes GL. Methods of Inactivation of SARS-CoV-2 for Downstream Biological Assays. J Infect Dis. 2020;222(9):1462-7. doi: 10.1093/infdis/jiaa507. PubMed PMID: 32798217; PMCID: PMC7529010.
Henson BS, Wong DT. Collection, storage, and processing of saliva samples for downstream molecular applications. Methods Mol Biol. 2010;666:21-30. doi: 10.1007/978-1-60761-820-1_2. PubMed PMID: 20717775.
Brouwer PJM, Caniels TG, van der Straten K, Snitselaar JL, Aldon Y, Bangaru S, Torres JL, Okba NMA, Claireaux M, Kerster G, Bentlage AEH, van Haaren MM, Guerra D, Burger JA, Schermer EE, Verheul KD, van der Velde N, van der Kooi A, van Schooten J, van Breemen MJ, Bijl TPL, Sliepen K, Aartse A, Derking R, Bontjer I, Kootstra NA, Wiersinga WJ, Vidarsson G, Haagmans BL, Ward AB, de Bree GJ, Sanders RW, van Gils MJ. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020;369(6504):643-50. doi: 10.1126/science.abc5902. PubMed PMID: 32540902; PMCID: PMC7299281.
Premkumar L, Segovia-Chumbez B, Jadi R, Martinez DR, Raut R, Markmann A, Cornaby C, Bartelt L, Weiss S, Park Y, Edwards CE, Weimer E, Scherer EM, Rouphael N, Edupuganti S, Weiskopf D, Tse LV, Hou YJ, Margolis D, Sette A, Collins MH, Schmitz J, Baric RS, de Silva AM. The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. 2020;5(48). doi: 10.1126/sciimmunol.abc8413. PubMed PMID: 32527802; PMCID: PMC7292505.
Honjo K, Russell RM, Li R, Liu W, Stoltz R, Tabengwa EM, Hua Y, Prichard L, Kornbrust AN, Sterrett S, Marques MB, Lima JL, Lough CM, McCarty TP, Ketas TJ, Hatziioannou T, Bieniasz PD, Redden DT, Moore JP, Goepfert PA, Heath SL, Hahn BH, Davis RS. Convalescent plasma-mediated resolution of COVID-19 in a patient with humoral immunodeficiency. Cell Rep Med. 2021;2(1):100164. doi: 10.1016/j.xcrm.2020.100164. PubMed PMID: 33521696; PMCID: PMC7817775.
MacMullan MA, Ibrayeva A, Trettner K, Deming L, Das S, Tran F, Moreno JR, Casian JG, Chellamuthu P, Kraft J, Kozak K, Turner FE, Slepnev VI, Le Page LM. ELISA detection of SARS-CoV-2 antibodies in saliva. Sci Rep. 2020;10(1):20818. doi: 10.1038/s41598-020-77555-4. PubMed PMID: 33257702; PMCID: PMC7705674.
Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, Claer L, Quentric P, Fadlallah J, Devilliers H, Ghillani P, Gunn C, Hockett R, Mudumba S, Guihot A, Luyt CE, Mayaux J, Beurton A, Fourati S, Bruel T, Schwartz O, Lacorte JM, Yssel H, Parizot C, Dorgham K, Charneau P, Amoura Z, Gorochov G. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med. 2021;13(577). doi: 10.1126/scitranslmed.abd2223. PubMed PMID: 33288662; PMCID: PMC7857408.
Varadhachary A, Chatterjee D, Garza J, Garr RP, Foley C, Letkeman AF, Dean J, Haug D, Breeze J, Traylor R, Malek A, Nath R, Linbeck L. Salivary anti-SARS-CoV-2 IgA as an accessible biomarker of mucosal immunity against COVID-19. medRxiv. 2020. doi: 10.1101/2020.08.07.20170258. PubMed PMID: 32817976; PMCID: PMC7430621.
Cervia C, Nilsson J, Zurbuchen Y, Valaperti A, Schreiner J, Wolfensberger A, Raeber ME, Adamo S, Weigang S, Emmenegger M, Hasler S, Bosshard PP, De Cecco E, Bachli E, Rudiger A, Stussi-Helbling M, Huber LC, Zinkernagel AS, Schaer DJ, Aguzzi A, Kochs G, Held U, Probst-Muller E, Rampini SK, Boyman O. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol. 2021;147(2):545-57 e9. doi: 10.1016/j.jaci.2020.10.040. PubMed PMID: 33221383; PMCID: PMC7677074.
Tosif S, Neeland MR, Sutton P, Licciardi PV, Sarkar S, Selva KJ, Do LAH, Donato C, Quan Toh Z, Higgins R, Van de Sandt C, Lemke MM, Lee CY, Shoffner SK, Flanagan KL, Arnold KB, Mordant FL, Mulholland K, Bines J, Dohle K, Pellicci DG, Curtis N, McNab S, Steer A, Saffery R, Subbarao K, Chung AW, Kedzierska K, Burgner DP, Crawford NW. Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19. Nat Commun. 2020;11(1):5703. doi: 10.1038/s41467-020-19545-8. PubMed PMID: 33177504; PMCID: PMC7658256.
Brandtzaeg P. Secretory immunity with special reference to the oral cavity. J Oral Microbiol. 2013;5. doi: 10.3402/jom.v5i0.20401. PubMed PMID: 23487566; PMCID: PMC3595421.
Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol. 2011;29:273-93. doi: 10.1146/annurev-immunol-031210-101317. PubMed PMID: 21219173; PMCID: PMC3064559.
Gronblad EA. Concentration of immunoglobulins in human whole saliva: effect of physiological stimulation. Acta Odontol Scand. 1982;40(2):87-95. doi: 10.3109/00016358209041120. PubMed PMID: 6954831.
Zhou D, Chan JF, Zhou B, Zhou R, Li S, Shan S, Liu L, Zhang AJ, Chen SJ, Chan CC, Xu H, Poon VK, Yuan S, Li C, Chik KK, Chan CC, Cao J, Chan CY, Kwan KY, Du Z, Lau TT, Zhang Q, Zhou J, To KK, Zhang L, Ho DD, Yuen KY, Chen Z. Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies. Cell Host Microbe. 2021;29(4):551-63 e5. doi: 10.1016/j.chom.2021.02.019. PubMed PMID: 33657424; PMCID: PMC7904446.
Chodick G, Tene L, Patalon T, Gazit S, Tov AB, Cohen D, Muhsen K. The effectiveness of the first dose of BNT162b2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world evidence. medRxiv. 2021; doi: 10.1101/2021.01.27.21250612.
Levine-Tiefenbrun M, Yelin I, Katz R, Herzel E, Golan Z, Schreiber L, Wolf T, Nadler V, Ben-Tov A, Kuint J, Gazit S, Patalon T, Chodick G, Kishony R. Decreased SARS-CoV-2 viral load following vaccination. medRxiv preprint. 2021; doi: 10.1101/2021.02.06.21251283.
Piccoli L, Park YJ, Tortorici MA, Czudnochowski N, Walls AC, Beltramello M, Silacci-Fregni C, Pinto D, Rosen LE, Bowen JE, Acton OJ, Jaconi S, Guarino B, Minola A, Zatta F, Sprugasci N, Bassi J, Peter A, De Marco A, Nix JC, Mele F, Jovic S, Rodriguez BF, Gupta SV, Jin F, Piumatti G, Lo Presti G, Pellanda AF, Biggiogero M, Tarkowski M, Pizzuto MS, Cameroni E, Havenar-Daughton C, Smithey M, Hong D, Lepori V, Albanese E, Ceschi A, Bernasconi E, Elzi L, Ferrari P, Garzoni C, Riva A, Snell G, Sallusto F, Fink K, Virgin HW, Lanzavecchia A, Corti D, Veesler D. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology. Cell. 2020;183(4):1024-42 e21. doi: 10.1016/j.cell.2020.09.037. PubMed PMID: 32991844; PMCID: PMC7494283.
Finkelstein MT, Mermelstein AG, Parker Miller E, Seth PC, Stancofski ED, Fera D. Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies. Viruses. 2021;13(1). doi: 10.3390/v13010134. PubMed PMID: 33477902; PMCID: PMC7833398.
Seaton KE, Deal A, Han X, Li SS, Clayton A, Heptinstall J, Duerr A, Allen MA, Shen X, Sawant S, Yates NL, Spearman P, Churchyard G, Goepfert PA, Maenza J, Gray G, Pantaleo G, Polakowski L, Robinson HL, Grant S, Randhawa AK, Huang Y, Morgan C, Grunenberg N, Karuna S, Gilbert PB, McElrath MJ, Huang Y, Tomaras GD, Niaid Hiv Vaccine Trials Network ST. Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans. NPJ Vaccines. 2021;6(1):56. doi: 10.1038/s41541-021-00305-8. PubMed PMID: 33859204; PMCID: PMC8050318.