SARS-CoV-2-Neutralizing Humoral IgA Response Occurs Earlier but Is Modest and Diminishes Faster than IgG Response

Abstract

Secretory dimeric immunoglobulin A (IgA) plays an important role in preventing the invasion of foreign objects by its neutralizing activity on mucosal surfaces, while monomeric serum IgA is thought to relate to the phagocytic immune system activation. Here, we report that individuals with the novel coronavirus disease (COVID-19) developed both systemic neutralizing IgG (nIgG) and IgA (nIgA) active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Immunogenicity and safety of single booster dose of KD-414 inactivated COVID-19 vaccine in adults: An open-label, single-center, non-randomized, controlled study in Japan

“…This suggests that the neutralizing activity after vaccination with KD-414 is largely due to the amount of IgG-S in the sera of booster-vaccinated participants. 18 IgM-S was detected in many participants after the primary series of BNT162b2 (P D7 ) (Supp. Table).…”

Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses

“… 67 , 68 , 69 , 70 The importance of mucosal secretory IgA (sIgA) in pathogen-specific responses against respiratory viral infections has long been appreciated for influenza viruses, 65 , 71 RSV, 72 , 73 and more recently SARS-CoV-2. 74 , 75 …”

Promises and challenges of mucosal COVID-19 vaccines

“…Limited induction of mucosal immunity coupled with lower accessibility of serum IgG to the upper respiratory tract likely leaves one vulnerable for re-infection. Indeed, intramuscular COVID-19 vaccinations, so far, have failed to induce a sustained IgA response in the nasal and oral cavities [ [52] , [53] , [54] ]. In a matched case control study, breakthrough infections assessed within 2–4 weeks after the second dose mRNA vaccination were shown to be associated with lower levels of serum IgA (but not IgG) in study participants compared to those who remain uninfected, suggesting IgA responses may be important in preventing breakthrough infections [ 52 ].…”

“…Furthermore, there may be limitations to our ability to provide mucosal protection against SARS-CoV-2, even with an optimal vaccine formation. Even though natural route infection with SARS-CoV-2 apparently induces superior immune protection at mucosal surfaces than intra-muscular vaccination [ [52] , [53] , [54] , [58] , [59] ], it also provides limited protection against re-infection. Indeed, many individuals experience multiple re-infections with SARS-CoV-2 [ [94] , [95] ], some only months after their initial infection [ 94 ].…”