mRNA COVID-19 vaccines induce high antibody titers with significant neutralizing potency in saliva

Scientists from the USA and Canada have recently demonstrated that the dynamics of antibody response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) vaccines are different.

While natural infection induces IgG- and IgA-specific antibodies with neutralizing activity in the saliva and plasma, mRNA-based COVID-19 vaccines induce high titers of IgG-specific antibodies with significant neutralizing potency in saliva. The study is currently available on the medRxiv* preprint server.


SARS-CoV-2, the causative pathogen of COVID-19, is an enveloped RNA virus that primarily attacks the nasopharyngeal and oral cavity mucosa to initiate infection. Thus, intranasal vaccines that induce mucosal antibodies are expected to offer early protection against the invading virus compared to intramuscular vaccines that mostly induce systemic antibodies.

In the USA, two mRNA-based COVID-19 vaccines (Pfizer/BioNTech and Moderna) and one human adenovirus vector-based COVID-19 vaccine (Johnson & Johnson/Janssen Pharmaceuticals) have received emergency use approval. All these vaccines are administered intramuscularly, with mRNA vaccines having a two-dose regimen and viral vector vaccines having a single-dose regimen. In both clinical trials and real-world setups, these vaccines have shown high efficacy in inducing robust systemic neutralizing antibodies and T cell response and providing protection against symptomatic COVID-19.

In the current study, the scientists have examined whether these vaccines are capable of inducing mucosal antibodies against SARS-CoV-2. They have measured the levels of IgG- and IgA-specific anti-spike receptor binding domain (RBD) antibodies in the plasma and saliva samples taken from individuals who have received either of these vaccines or previously had SARS-CoV-2 infection (convalescent individuals).

Antibody response following vaccination or infection

SARS-CoV-2 infection

The majority of convalescent plasma samples (89%) exhibited detectable levels of IgA-specific anti-spike RBD antibodies. Similarly, IgG-specific anti-RBD antibodies were detected in all convalescent plasma samples. In contrast, only 25% of convalescent saliva samples exhibited detectable levels of IgG-specific antibodies. While salivary IgA antibodies showed non-specific binding to spike RBD, salivary IgG antibodies showed high specificity. A significantly high neutralizing antibody titer was also detected in convalescent plasma and saliva samples.

COVID-19 vaccination

Among participants who had received the viral vector vaccine, about 68% and 29% exhibited detectable levels of IgG- and IgA-specific anti-RBD antibodies in the plasma samples, respectively, at day 29 post-vaccination. In a separate set of plasma samples collected at day 72 post-vaccination, IgG antibodies were detected in 33% of vaccine recipients, whereas the level of IgA antibodies reduced significantly. Regarding neutralizing antibodies, significantly high titers were detected at days 29 and 71 post-vaccination. In these patients, a low of IgG antibodies were detected in saliva samples at day 29 post-vaccination.     

In mRNA-vaccinated participants, significantly high levels of IgG antibodies were detected in saliva samples even at day 60 post-vaccination. A small proportion of the vaccine recipients also showed detectable IgA antibodies in the saliva. The IgG antibody levels detected after a single vaccine dose was comparable to those observed in convalescent saliva samples.    

Overall, the study findings revealed that natural infection induces the production of IgG- and IgA-specific anti-RBD antibodies with neutralizing activity in both saliva and plasma. Regarding COVID-19 vaccines, the two-dose regimen of mRNA vaccines induced more robust binding and neutralizing antibody responses in plasma and saliva compared to the single-dose regimen of the viral vector vaccine. The levels of mRNA vaccine-induced IgG antibodies with neutralizing activity in saliva were comparable to that observed in natural infection. The individuals with high levels of salivary IgA antibodies showed a peak in neutralizing antibody titers after the second vaccine dose.   

Study significance

The study findings reveal that intramuscularly administered mRNA-based COVID-19 vaccines can induce mucosal antibody response, in addition to inducing robust systemic antibody response. As mentioned by the scientists, the mucosal antibody response could be due to circulating spike proteins that are generated by the vaccines and remain detectable in the blood for several days post-vaccination. Another reason could be passive transudation of neutralizing antibodies.  

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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