tetano
Editor, Senior Moderator
J Infect Dis
. 2025 Apr 29:jiaf176.
doi: 10.1093/infdis/jiaf176. Online ahead of print. Mucosal and Systemic Antibody Responses After Boosting With a Bivalent Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine
Robert L Atmar[SUP] 1 [/SUP], Kirsten E Lyke[SUP] 2 [/SUP], Christine M Posavad[SUP] 3 4 [/SUP], Meagan E Deming[SUP] 2 [/SUP], Rebecca C Brady[SUP] 5 [/SUP], David Dobrzynski[SUP] 6 [/SUP], Srilatha Edupuganti[SUP] 7 [/SUP], Mark J Mulligan[SUP] 8 [/SUP], Richard E Rupp[SUP] 9 [/SUP], Christina A Rostad[SUP] 10 [/SUP], Lisa A Jackson[SUP] 11 [/SUP], Judith M Martin[SUP] 12 [/SUP], Mallory C Shriver[SUP] 2 [/SUP], Kumaravel Rajakumar[SUP] 12 [/SUP], Rhea N Coler[SUP] 13 14 [/SUP], Hana M El Sahly[SUP] 1 [/SUP], Angelica C Kottkamp[SUP] 8 [/SUP], Angela R Branche[SUP] 6 [/SUP], Robert W Frenck[SUP] 5 [/SUP], Christine Johnston[SUP] 3 4 15 [/SUP], Tara M Babu[SUP] 15 [/SUP], Martín Bäcker[SUP] 16 [/SUP], Janet I Archer[SUP] 17 [/SUP], Sonja Crandon[SUP] 18 [/SUP], Aya Nakamura[SUP] 18 [/SUP], Seema U Nayak[SUP] 18 [/SUP], Daniel Szydlo[SUP] 19 [/SUP], Clara P Dominguez Islas[SUP] 4 [/SUP], Elizabeth R Brown[SUP] 4 [/SUP], Sarah E O'Connell[SUP] 20 [/SUP], David C Montefiori[SUP] 21 22 [/SUP], Amanda Eaton[SUP] 22 [/SUP], Kathleen M Neuzil[SUP] 2 [/SUP], David S Stephens[SUP] 7 [/SUP], John H Beigel[SUP] 18 [/SUP], Marcela Pasetti[SUP] 2 [/SUP], Paul C Roberts[SUP] 18 [/SUP]
Affiliations
Background: Mucosal immunity plays a critical role in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and replication. Understanding the capacity of coronavirus disease 2019 (COVID-19) vaccines to elicit both mucosal and systemic antibodies could help optimize vaccination strategies.
Methods: We conducted an open-label, phase 1/2 adaptive-design clinical trial to evaluate the safety and immunogenicity of COVID-19 immunizations. Healthy adults received 2 priming doses of mRNA-1273, a booster dose of mRNA-1273, and a second booster of bivalent (WA-1 and BA.4/BA.5) mRNA-1273.222. Adverse event data were collected. Serum and mucosal immunity were evaluated.
Results: One hundred six persons were enrolled. Thirty received all 4 study-related vaccine doses. All vaccines were well tolerated, with injection site pain, malaise, myalgias, and headache being the most frequently reported symptoms. Among those who received a second booster, 24 of 30 (80%) had serological evidence of SARS-CoV-2 infection. Following the second booster, increases in geometric mean binding and pseudovirus neutralization antibody titers to the ancestral strain and BA.1 and BA.5 variants were observed. Increases in mucosal immunoglobulin G and immunoglobulin A (IgA) antibodies in nasal and salivary samples were observed in both previously infected and infection-naive participants, although prior infection markedly boosted virus-specific mucosal IgA responses.
Conclusions: The mRNA-1273.222 booster vaccine was safe and immunogenic and induced mucosal antibody responses in previously infected and infection-naive persons.
Clinical trials registration: NCT04889209.
Keywords: COVID-19; SARS-CoV-2; booster; immunogenicity; vaccine.
. 2025 Apr 29:jiaf176.
doi: 10.1093/infdis/jiaf176. Online ahead of print. Mucosal and Systemic Antibody Responses After Boosting With a Bivalent Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine
Robert L Atmar[SUP] 1 [/SUP], Kirsten E Lyke[SUP] 2 [/SUP], Christine M Posavad[SUP] 3 4 [/SUP], Meagan E Deming[SUP] 2 [/SUP], Rebecca C Brady[SUP] 5 [/SUP], David Dobrzynski[SUP] 6 [/SUP], Srilatha Edupuganti[SUP] 7 [/SUP], Mark J Mulligan[SUP] 8 [/SUP], Richard E Rupp[SUP] 9 [/SUP], Christina A Rostad[SUP] 10 [/SUP], Lisa A Jackson[SUP] 11 [/SUP], Judith M Martin[SUP] 12 [/SUP], Mallory C Shriver[SUP] 2 [/SUP], Kumaravel Rajakumar[SUP] 12 [/SUP], Rhea N Coler[SUP] 13 14 [/SUP], Hana M El Sahly[SUP] 1 [/SUP], Angelica C Kottkamp[SUP] 8 [/SUP], Angela R Branche[SUP] 6 [/SUP], Robert W Frenck[SUP] 5 [/SUP], Christine Johnston[SUP] 3 4 15 [/SUP], Tara M Babu[SUP] 15 [/SUP], Martín Bäcker[SUP] 16 [/SUP], Janet I Archer[SUP] 17 [/SUP], Sonja Crandon[SUP] 18 [/SUP], Aya Nakamura[SUP] 18 [/SUP], Seema U Nayak[SUP] 18 [/SUP], Daniel Szydlo[SUP] 19 [/SUP], Clara P Dominguez Islas[SUP] 4 [/SUP], Elizabeth R Brown[SUP] 4 [/SUP], Sarah E O'Connell[SUP] 20 [/SUP], David C Montefiori[SUP] 21 22 [/SUP], Amanda Eaton[SUP] 22 [/SUP], Kathleen M Neuzil[SUP] 2 [/SUP], David S Stephens[SUP] 7 [/SUP], John H Beigel[SUP] 18 [/SUP], Marcela Pasetti[SUP] 2 [/SUP], Paul C Roberts[SUP] 18 [/SUP]
Affiliations
- PMID: 40298376
- DOI: 10.1093/infdis/jiaf176
Background: Mucosal immunity plays a critical role in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and replication. Understanding the capacity of coronavirus disease 2019 (COVID-19) vaccines to elicit both mucosal and systemic antibodies could help optimize vaccination strategies.
Methods: We conducted an open-label, phase 1/2 adaptive-design clinical trial to evaluate the safety and immunogenicity of COVID-19 immunizations. Healthy adults received 2 priming doses of mRNA-1273, a booster dose of mRNA-1273, and a second booster of bivalent (WA-1 and BA.4/BA.5) mRNA-1273.222. Adverse event data were collected. Serum and mucosal immunity were evaluated.
Results: One hundred six persons were enrolled. Thirty received all 4 study-related vaccine doses. All vaccines were well tolerated, with injection site pain, malaise, myalgias, and headache being the most frequently reported symptoms. Among those who received a second booster, 24 of 30 (80%) had serological evidence of SARS-CoV-2 infection. Following the second booster, increases in geometric mean binding and pseudovirus neutralization antibody titers to the ancestral strain and BA.1 and BA.5 variants were observed. Increases in mucosal immunoglobulin G and immunoglobulin A (IgA) antibodies in nasal and salivary samples were observed in both previously infected and infection-naive participants, although prior infection markedly boosted virus-specific mucosal IgA responses.
Conclusions: The mRNA-1273.222 booster vaccine was safe and immunogenic and induced mucosal antibody responses in previously infected and infection-naive persons.
Clinical trials registration: NCT04889209.
Keywords: COVID-19; SARS-CoV-2; booster; immunogenicity; vaccine.