Pillar 1
Immunology & Vaccine Protection

Establishing immunity in the oral and nasal cavities is an important first line of defense against the development of symptoms and illness due to COVID-19 and associated variants, which results from infection of the upper airway. CoVaRR-Net funded researchers, Jennifer Gommerman at University of Toronto, Anne-Claude Gingras at Lunenfeld Tanenbaum Research Institute, and their colleagues have published findings in Mucosal Immunology to support the idea that oral mucosal immunity against COVID-19 may play an important role in protecting against breakthrough infections as part of the overall immune response to infection and vaccination.

Immunity to a pathogen depends partly on the body’s development of disease-specific antibodies that can bind and neutralize or destroy toxins or disease carrying organisms.  Different antibody classes are distinguished by differences in their function in different tissue and types of immune responses. While both IgA and IgG antibodies are prevalent within the blood vessels, IgA is more prevalent and can be detected in secretions like tears, mucous and saliva.

COVID-19 vaccines were designed to help our bodies develop antibodies against the SARS-CoV-2 Spike protein and its Receptor Binding Domain (RBD) to protect us against infection and severe disease. The study authors and others have shown that antibodies against SARS-CoV-2 could be detected in the saliva of infected patients. These antibodies are important for providing protective immunity that can help prevent infection by neutralizing the virus. Whether COVID-19 vaccines delivered via an intramuscular route elicited an antibody response in the oral mucosa remained unclear, which is what this study aimed to address.

To better understand the mucosal immune response following intramuscular COVID-19 vaccination, the authors collected blood and saliva samples from adult participants who received 2 doses of mRNA COVID-19 vaccines, and measured levels of anti-SARS-CoV-2 antibodies in each biofluid. Their analyses revealed that:

  • Subjects who were vaccinated with mRNA COVID-19 vaccines had antibodies against Spike and RBD in their saliva.
  • Following the first dose of an mRNA COVID-19 vaccine, almost all participants showed evidence of a mucosal immune response to intramuscular vaccination.
  • Following the second dose of an mRNA COVID-19 vaccine, IgG antibodies in the serum and saliva were boosted, while IgA was not. In fact, IgA titers remained detectable in only 30% of subjects.
  • 6 months post-dose 2, there was a steady decline of IgG levels in saliva, although titers were still detectable. IgA and secretory component (indicative of locally produced antibodies) on the other hand remained more stable in comparison.

Furthermore, when looking at antibody responses in participants who experienced SARS-CoV-2 variant breakthrough infections compared to those who did not experience an infection, IgG antibody levels were comparable. However, levels of vaccine-induced IgA antibodies in serum detected at 2-4 weeks after dose 2 were reduced in the breakthrough group.

Taken together, these data suggest that higher levels of saliva-specific IgA antibodies, that can be boosted by COVID-19 vaccination, may help to protect against subsequent infections.

Ongoing work within CoVaRR-Net Pillar 1 aims to expand on these findings by looking at mucosal immunity against COVID-19 variant induced breakthrough infections as well as understanding mucosal immune responses to vaccination and infection in pediatric populations.

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Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection. Salma Sheikh-Mohamed, Baweleta Isho, Gary Y.C. Chao, Michelle Zuo, Carmit Cohen, Yaniv Lustig, George R. Nahass, Rachel E. Salomon-Shulman, Grace Blacker, Mahya Fazel-Zarandi, Bhavisha Rathod, Karen Colwill, Alainna Jammal, Zhijie Li, Keelia Quinn de Launay, Alyson Takaoka, Julia Garnham Takaoka, Anjali Patel, Christine Fahim, Aimee Paterson, Angel Xinliu Li Nazrana Haq, Shiva Barati, Lois Gilbert, Karen Green, Mohammad Mozafarihashjin, Philip Samaan, Patrick Budylowski, Walter L. Siqueira, Samira Mubareka, Mario Ostrowski, James M. Rini, Olga L. Rojas, Irving L. Weissman, Michael Caspi Tal, Allison McGeer, Gili Regev-Yochay, Sharon Straus, Anne Claude-Gingras, Jennifer L. Gommerman. Mucosal Immunology. 2022.04.25.00511.  https://www.nature.com/articles/s41385-022-00511-0#ref-CR2