Natural and hybrid immunity dynamics in South African mothers

In a recent study posted to the medRxiv* preprint server, researchers evaluated natural and hybrid immunity after four coronavirus disease 2019 (COVID-19) waves in South Africa.

Study: Natural and hybrid immunity following four COVID-19 waves in a South African cohort. Image Credit: Andrii Vodolazhskyi/Shutterstock
Study: Natural and hybrid immunity following four COVID-19 waves in a South African cohort. Image Credit: Andrii Vodolazhskyi/Shutterstock


Infection with ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confers partial protection against reinfection with the same strain and closely related variants. Protection against reinfection might result from the presence of anti-receptor-binding domain (anti-RBD) antibodies and antigen-specific T cells.

Reports indicate that primary vaccination with COVID-19 vaccines provides poor protection against symptomatic infection with the Omicron variant. In the context of natural infection, the association of antibody responses and subsequent protection against reinfection is poorly understood since most studies have focused on vaccine-induced immune responses.

Nonetheless, vaccinating convalescent individuals results in more robust protection than infection or vaccination alone. This type of immunity has been referred to as hybrid immunity, and it augments the breadth of protection against different variants, probably due to immune maturation.

About the study

In the present study, researchers investigated natural and hybrid immune responses in a cohort of South African mothers. The study population comprised a convenience sample of mothers from a peri-urban community throughout the four COVID-19 waves. South Africa witnessed four COVID-19 waves, first at the onset of the pandemic, and the subsequent surges were driven by SARS-CoV-2 Beta (second), Delta (third), and Omicron (fourth) variants.

The research team measured serologic responses against SARS-CoV-2 in serum samples following each wave. They tested for immunoglobulin G (IgG) antibodies against the spike (S) protein of ancestral strain, Beta, Delta, or Omicron variant. Participants were excluded from seroprevalence assessment upon vaccination.

Risk factors linked to seropositivity were identified using generalized estimating equations (GEE). The GEE models were adjusted for age, marital status, human immunodeficiency virus (HIV) infection, educational qualification, employment, household size and income, asthma, and smoking.


The study population comprised 339 mothers, predominantly from low socioeconomic status. Smoking was self-reported by 124 subjects, and 69 participants had HIV infection. During the study period, 18 individuals contracted SARS-CoV-2, and three cases were hospitalized due to COVID-19; no deaths were recorded.

Two subjects received the Janssen’s Ad.26COV2.S vaccine before their second sampling (during the Beta wave). Before the third wave, 19 mothers were vaccinated with Ad.26COV.2S and 76 with Pfizer’s BNT162b2 vaccine. About 45.4% (154) of the participants were vaccinated with either vaccine before the fourth wave.

Seropositivity was recorded in more than half of the study population after the first COVID-19 wave. Seropositivity among non-vaccinated subjects increased to 74.3% after the Beta wave, 89.8% after the third wave, and 97.9% after the fourth wave. Only five participants were seronegative throughout the four waves.

In unadjusted analysis, maternal weight, HIV infection, and age were positively associated with seropositivity, whereas smoking was inversely associated. After adjustment, individuals living in crowded households showed higher odds of seropositivity, while smoking was associated with seronegativity.

Seroconversion was evident in 52% of seronegative mothers after the first and second COVID-19 waves. Following the third and fourth waves, 66% and 77% of individuals showed seroconversion, respectively. The highest anti-S IgG concentrations among the non-vaccinated mothers were observed post-Omicron wave. Moreover, antibody concentrations were higher with each wave in mothers who were seropositive in preceding COVID-19 waves than seronegative subjects.

The probability of boosting in participants with low pre-wave IgG titers was 53% during the second wave, 68%, and 84% during the third and fourth waves, respectively. In contrast, boosting rates in those with the high antibody titers were low at 17%, 39%, and 29% during the Beta, Delta, and Omicron waves, respectively. The authors noted that substantially higher pre-wave anti-ancestral-S protein IgG titers were required before the Omicron wave to confer 50% protection against infection.

Among the vaccinated subjects, 87.7% exhibited seropositivity before vaccination. Antibody titers against all S protein variants after partial or complete vaccination with the BNT162b2 vaccine were significantly higher in mothers with pre-vaccination seropositivity than in seronegative individuals. IgG titers did not increase after the second vaccine dose in those with pre-vaccination seropositivity, albeit a second dose increased IgG levels in seronegative mothers.


The authors observed a high seroprevalence in a low-income peri-urban community in South Africa. Seropositivity upon natural infection conferred protection against SARS-CoV-2 Beta and Delta variants, but substantially high antibody titers were required for protection against Omicron.

Vaccination of seropositive mothers resulted in greater anti-S protein IgG concentrations than seronegative subjects. The authors noted that most seropositive-vaccinated mothers were protected against the Omicron variant. The results indicated that vaccination of seropositive people might confer sufficient immunity against known and related SARS-CoV-2 variants.

*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:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.


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