Neutralization and Anti-S Antibody Titers in SARS-CoV-2 Boosted Adults in Mexico: A Comparison Across Five Vaccine Types.

Introduction: The World Health Organization (WHO) recommends the administration of booster doses after completing primary vaccination. Yet, recommendations are largely based on a small set of vaccines, with little information about vaccine mixes used in low and middle-income countries. We aimed to estimate the titers of anti-protein S (RBD) IgG antibodies and neutralization in Mexican adults with a complete vaccination scheme without a booster or with one of five different booster types (heterologous or homologous) to assess immunogenic response. Materials and Methods: We included data from 2953 adults aged 18 years and older, representing 49.1 million Mexicans, from the National Health and Nutrition Survey (ENSANUT) 2022. We included five primary schemes: BNT162b2, AZD1222, Ad5-nCoV, Gam-COVID-Vac, and CoronaVac. A booster dose was defined as an additional dose beyond the primary scheme and classified as homologous or heterologous based on three vaccine platforms: mRNA, viral vector, and inactivated virus. For each primary scheme, we estimated marginal means of anti-protein S geometric mean titers (GMTs) with 95% CI in each group (no booster, heterologous booster, or homologous booster) adjusted for age, time since the last dose, and prior natural infection using anti-protein N antibodies seropositivity as a proxy using a multivariable linear regression. Then, we estimated the percentage of neutralizing antibodies for the original SARS-CoV-2 strain. Results: We observed that the highest anti-protein S GMTs were in the group that received a heterologous booster with BNT162b2, AZD1222, Ad5-nCoV, or CoronaVac; the group without a booster showed the lowest GMTs. All groups in the primary schemes had 90% or more inhibition for the original SARS-CoV-2 strain, except in the AZD1222 and Ad5-nCoV groups without a booster. Conclusions: Boosters increased GMTs for all people, independently of their primary vaccine scheme. Yet, our findings suggest that a heterologous booster produced higher titers against SARS-CoV-2 protein S. Efforts should be made to reach people who received AZD1222 and Ad5-nCoV as their primary scheme and did not get boosted, as neutralization in those groups was particularly low.