Study investigates population immunity to SARS-CoV-2 through heterogenous pathways

In Mexico, a middle-income country, five different coronavirus disease 2019 (COVID-19) vaccines have been available to the population. A new study demonstrates vaccine-specific differences in the antibody responses and memory B-cell immunity in a sample population comprising of 197 vaccinated individuals.

Study: Antibody and memory B-cell immunity in a heterogeneously SARS-CoV-2 infected and vaccinated population. Image Credit: Moab Republic/ShutterstockStudy: Antibody and memory B-cell immunity in a heterogeneously SARS-CoV-2 infected and vaccinated population. Image Credit: Moab Republic/Shutterstock

A preprint version of the study, which is yet to undergo peer review, is available on the medRxiv* server.

Variable immunity levels in populations

In the COVID-19 pandemic, several COVID-19 vaccines have been authorized for vaccination. Most of the vaccines, developed using distinct platforms, are based on a variant very similar to the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain from Wuhan, China. Different vaccines have different immunogenic potentials and abilities to prevent infection and severe outcomes. Vaccine waning has been a common phenomenon for all vaccines. Furthermore, highly transmissible, immune-evading variants have emerged.

A definitive measure of immune protection against SARS-CoV-2 infection is the level of neutralizing antibodies in an individual. The neutralizing antibodies target the SARS-CoV-2 spike protein. This has led to spike protein evolution due to selective pressure on SARS-CoV-2. Also, the recent Omicron variant is particularly resistant to neutralizing antibodies, thus,causing breakthrough infections.

Most of the studies on vaccine-induced neutralizing antibody responses against SARS-CoV-2 have focused on single vaccines available in high-income countries. The vaccines available in low- and middle-income countries are not uniform. Thus, immunity levels in such populations are also expected to be variable. The data on these variabilities will help policymakers to make informed recommendations concerning booster doses and interventions to avoid the spread of the disease.

Vaccination in Mexico

In this study, the investigators conducted genomic surveillance of SARS-CoV-2 variants from February 2020 to January 2022 in Mexico. Most of the variants observed around the world were also observed in Mexico. However, Mexico also reported a highly prevalent B.1.1.519 variant which did not spread globally. Currently, the B.1.1.529 Omicron variant is dominant in Mexico.

Five COVID-19 vaccines have been made available in Mexico from December 2020 to spring 2021 - BNT162b2 mRNA vaccine; adenovirus-based vaccines ChAdOx1-S, Sputnik V, and single-dose Ad5-nCoV; and an inactivated whole virus vaccine, CoronaVac.

This study enrolled 197 individuals - 29 received BNT162b2, 38 received ChAdOx1-S, 57 received Sputnik V, 42 received Ad5-nCoV, and 31 received CoronaVac. Eighty individuals (40.6%) had a prior SARS-CoV-2 infection. Blood samples were collected from all individuals between 0.5 to 4.7 months post-vaccination.

Immunity conferred by COVID-19 vaccines

The investigators performed neutralization assays using pseudoviruses to compare the vaccine-elicited neutralizing antibodies. The pseudoviruses were engineered to carry the spike protein from the wild-type SARS-CoV-2 variant or the other variants that emerged in Mexico.

The BNT162b2 mRNA vaccine-elicited median 50% neutralizing levels (NT50) were 2,836 against the wild-type SARS-CoV-2 variant in individuals without prior SARS-CoV-2 infection. These levels were 6-fold lower in individuals who received the CoronaVac vaccine. The median NT50 was 542 in individuals who received CoronaVac which was similar for the single-dose Ad5-nCoV vaccine. The ChAdOx1-S and Sputnik V vaccines induced median NT50 of 705 and 1,013. For all the vaccines, the neutralizing antibody levels in recipient plasma reduced for variants that subsequently emerged in Mexico. The reduction was 1.2- to 4.6-fold for the Alpha and Gamma variants, 4.8- to 10.8-fold for the Beta variants, and 2.8- to 5.1-fold for the Delta variant.

For many individuals, neutralizing antibody levels in recipient plasma against the Beta and Delta variants were below the detection range, noticeably for the CoronaVac vaccinees. The blood samples from uninfected BNT162b2, AstraZeneca, Sputnik, Ad5-nCoV, and CoronaVac vaccinees had undetectable neutralizing activity against the Omicron variant.

The neutralizing antibody levels in the infected and vaccinated individuals were 2.3-fold to 23-fold higher than the uninfected and vaccinated individuals. The increase was seen for the emergent variants as well. The median NT50 values for the infected vaccinees were 6,593 for BNT162b2, 10,893 for ChAdOx1-S, 18,634 for Sputnik V, 12,462 for Ad5-nCoV, and 2,133 for CoronaVac. The median NT50 values for the infected vaccinees against the Omicron variant were 808 for BNT162b2, 816 for ChAdOx1-S, 1,407 for Sputnik V, 1,144 for Ad5-nCoV, and 328 for CoronaVac.

In this study, the investigators also measured the percentage of a subset of B cells in the vaccinees. These B cells were memory cells specific to the spike protein or the receptor-binding domain. The median percentage of spike-specific B cells in previously uninfected individuals was 0.022% in BNT162b2 vaccinees, 0.003% in CoronaVac vaccinees, 0.006% in ChAdOx1-S vaccinees, 0.007% in Sputnik V vaccinees, and 0.004% in Ad5-nCoV vaccinees. Individuals with a prior infection had higher Spike-specific memory B cells with median percentages of 0.073% for BNT162b2 vaccinees, 0.18% for ChAdOx1-S vaccinees, 0.14% for Sputnik V vaccinees, 0.11% for Ad5-nCoV vaccinees, and 0.073% for CoronaVac vaccinees. Similar trends were observed with RBD-binding memory B cells. Importantly, the neutralizing antibody levels correlated with the memory B cells for all vaccines except for BNT162b2. They also correlated with spike binding antibodies.


The time between vaccination and sample collection varied between individuals. This makes it difficult to compare the vaccine platforms. Therefore, the investigators determined the change in antibody levels with time against the Delta and Omicron variants. There was a longitudinal variation observed in the neutralizing activity.


Appropriate serological assays can be useful in the prediction of mild versus severe outcomes and the probability of infection in a population. This can inform policymakers to devise health care strategies, in a resource-poor setting like Mexico, where booster shots can be administered to those that received vaccines that induced low levels of antibodies. This information can also guide wealthier nations to use different vaccine platforms and provide multiple options when confronting issues like vaccine distribution inequity, production limitations, and vaccine hesitancy among populations. According to this study, broad population immunity to SARS-CoV-2 will eventually be achieved, albeit through heterogeneous ways.

*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.

Journal reference:
Dr. Shital Sarah Ahaley

Written by

Dr. Shital Sarah Ahaley

Dr. Shital Sarah Ahaley is a medical writer. She completed her Bachelor's and Master's degree in Microbiology at the University of Pune. She then completed her Ph.D. at the Indian Institute of Science, Bengaluru where she studied muscle development and muscle diseases. After her Ph.D., she worked at the Indian Institute of Science, Education, and Research, Pune as a post-doctoral fellow. She then acquired and executed an independent grant from the DBT-Wellcome Trust India Alliance as an Early Career Fellow. Her work focused on RNA binding proteins and Hedgehog signaling.


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