Vaccination and Omicron BA.1/BA.2 Convalescence Enhance Systemic but Not Mucosal Immunity against BA.4/5

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Rising breakthrough infections with SARS-CoV-2 Omicron BA.4/5 highlight limitations of current vaccines.
• Systemic immunity has been studied, but mucosal immunity against SARS-CoV-2 remains under-evaluated.
• Mucosal immunity is critical for limiting viral entry and transmission.

Purpose of the Study:

• To investigate humoral and mucosal immune responses in vaccinated and/or convalescent individuals against SARS-CoV-2 Omicron BA.4/5.
• To compare neutralization activity in serum and saliva against wild-type SARS-CoV-2 and Omicron BA.4/5 variant.
• To evaluate the effectiveness of current vaccine strategies and explore potential improvements.

Main Methods:

• Cohort study of 92 individuals with diverse vaccination and convalescent histories.
• Analysis of serum and saliva samples for SARS-CoV-2 spike-specific IgG and IgA titers.
• Assessment of virus-neutralizing activity against wild-type SARS-CoV-2 and Omicron BA.4/5 using replication-competent virus.

Main Results:

• Vaccinated/convalescent cohorts showed the strongest neutralization against BA.4/5, but with an up to 11-fold reduction compared to wild-type.
• BA.1 convalescent and vaccinated nonconvalescent cohorts exhibited significantly weaker neutralization against BA.4/5.
• Salivary neutralization against wild-type virus was reduced against BA.4/5, even in subjects with strong responses to wild-type.

Conclusions:

• Current COVID-19 vaccines effectively induce humoral immunity but show reduced antiviral effectiveness against Omicron BA.4/5 in both serum and saliva.
• Vaccinated individuals who recovered from BA.2 infection showed the highest serum neutralization against BA.4/5, but this was not mirrored in saliva.
• Alternative vaccine strategies, such as mucosal boosters, are suggested to establish enhanced or sterilizing immunity against emerging SARS-CoV-2 variants.