Vaccine and/or natural infection-induced immune responses against SARS-CoV-2 omicron subvariants

In a recently published study bioRxiv* Preprint server, researchers comparatively assessed the neutralizing antibody (Ab) titers for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron VOC (variants of concern) subvariants BA.1, BA.2, BA.4/5 among individuals with a history of B.1 (D614G) strain infections, vaccinated individuals, or with hybrid (combined) immunity to breakthrough infections (BTI) and vaccinations with delta or gamma VOCs.

background

The continuous emergence of omicron sub-VOCs has compromised vaccine efficacy and justified the development of novel and updated anti-SARS-CoV-2 agents. Assessing the cross-neutralization of immunological responses induced by either vaccination or natural infection, or both, is crucial to guide policy making and improve preparedness for COVID-19.

About the study

In the present study, researchers compared BTI and/or vaccine-induced immune responses prior to Omicron with the novel Omicron subvariants BA.1, BA.2 and BA.4/5.

The team compared the neutralizing ability of sera collected from 58 unvaccinated and D614G-infected patients with coronavirus disease 2019 (COVID-19) (convalescent sera), 14 booster-vaccinated (three doses) individuals, and 16 vaccinated and delta-infected (n= 14) or gamma-infected (n=2) BTI patients against strains D614G, Delta and Omicron BA.1, BA.2, BA.4/5.

The unvaccinated individuals were infected between March and July 2020, and BTI patients were infected between July 15 and September 20, 2021. Triple COVID-19 vaccinees received a messenger ribonucleic acid (mRNA) booster dose between October 2021 and January 2022. COVID-19 diagnosis was confirmed by reverse transcription polymerase chain reaction (RT-PCR) for all patients.

Vero E6 cells and human embryonic kidney (HEK)293T angiotensin converting enzyme 2 (ACE2)- tTransmembrane protease, serine 2 (TMPRSS2) cells were used for cell culture experiments. Multiplex assays including SARS-CoV-2 antigens [nucleocapsid (N), spike (S), receptor-binding domain (RBD), N-terminal domain (NTD)] and S from other CoVs [SARS-CoV, Middle East respiratory syndrome CoV (MERS-CoV), OC43, HKU1] and influenza A hemagglutinin H3 were used to measure anti-SARS-CoV-2 immunoglobulin G (IgG) Ab titers.

Nasopharyngeal swabs (NPS) were obtained from participants for virologic assays and next-generation sequencing (NGS) was performed. Live virus neutralization assays and pseudotype-based human immunodeficiency virus (HIV) neutralization assays were performed to assess VOC and sub-VOC neutralization of SARS-CoV-2. The 50% tissue culture infectious dose (TCID₅₀), the half-maximal inhibitory concentration (IC₅₀) and the 50% neutralizing titer (NT₅₀) values ​​determined.

Results

All of Omicron’s sub-VOCs showed extensive immune evasion from all participants’ sera compared to D614G and Delta, albeit to varying degrees depending on the origin of the sera. BA.1. COVID-19 convalescents failed to neutralize Omicron BA.1 sub-VOC and partially neutralize Omicron BA.2 and BA.4/5. Sera from vaccinated individuals partially neutralized the Omicron BA.2 Sub-VOC but not BA.1 and BA.4/5.

BTI patient sera showed similar neutralizing titers for all Omicron sub-VOCs. BTI patient sera and convalescent sera showed the highest and lowest neutralization potential, respectively, for all of Omicron’s sub-VOCs. The NT₅₀The :AK ratios (AK avidity) were significantly higher in BTI patients than in convalescents.

Moderate COVID-19 convalescents showed better neutralization responses. BA.1 and BA.2 showed the greatest resistance or sensitivity to all sera. Omicron BA.5 evaded the neutralization responses of vaccinated individuals better than natural infection-induced and hybrid immunity-induced responses.

Among those recovering from COVID-19 NT₅₀ Geometric mean titers (GMT) for B.1 (125) and Delta (153) were comparable. Even at a serum concentration of 1:40, 33% and 39% of subjects failed to neutralize Omicron B.1 and Delta, respectively. The NT₅₀ GMTs for BA.2, BA.4, and BA.5 were 55, 37, and 60, respectively, significantly lower than those for B.1 and Delta.

BA.4 was significantly more resistant than BA.2 and BA.5 and could not be neutralized by 75% of the sera. N.T₅₀:Anti-S, NT₅₀The ratios of :anti-RBD and N50:anti-NTD were similar for B.1 and Delta and lower by a log10 micron BA.1. Among the boosted vaccinates is NT₅₀ GMT titers for B.1, Delta, BA.1, BA.4, and BA.5 were 247, 345, 51, 46, and 59, respectively.

In BTI patients, NT₅₀ GMTs for B.1, Gamma/Delta, Omicron BA.1 Sub-VOC, BA.2 Sub-VOC, BA.4 Sub-VOC and Omicron BA.5 Sub-VOC were 195, 330, 44, 71, 52 , and 88 and NT, respectively₅₀:Ab ratios were one log10 higher for B.1 and Delta than for Omicron sub-VOCs. Compare NT₅₀ values ​​of all sera (convalescents + vaccinates + BTI patients) showed a trend towards greater delta neutralization than B.1 and much less (1.5 log10) omicron sub-VOC neutralization.

Overall, the study results underscored the importance of COVID-19 vaccination in generating Abs with high cross-reactivity against SARS-CoV-2 VOCs and sub-VOCs, and showed that immunological imprinting by first-generation vaccines limits cross-infection, but not completely could end -neutralization.

*Important NOTE

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health behavior, or be treated as established information.