SARS-CoV-2 Omicron BA.5 neutralization in vaccinated individuals

In a recent study posted to the medRxiv* preprint server, researchers assessed the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 neutralization in SARS-CoV-2 vaccinated persons.

Study: Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without Omicron breakthrough infection. Image Credit: Ground Picture/Shutterstock
Study: Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without Omicron breakthrough infection. Image Credit: Ground Picture/Shutterstock

The SARS-CoV-2 Omicron clade has evolved into rapidly transmittable sub-lineages including BA.5, which proved to be more potent than BA.2 and BA.2. Various studies have reported that the neutralizing activity of the coronavirus disease 2019 (COVID-19) vaccines against BA.5 is lesser than that against BA.1 and BA.2, which necessitates an extensive study of vaccine effectiveness against BA.5 infections.

About the study

In the present study, researchers estimated the durability of the neutralizing antibody (nAb) response elicited by BNT162b2 COVID-19 vaccination among individuals with and without a history of SARS-CoV-2 Omicron BA.1 and BA.2 breakthrough infection.

The team obtained a total of 35 nasal and 291 serological samples from 27 healthcare workers (HCW) in Orleans, France. Samples were collected three to 21 times from each eligible participant over the course of the study. The team estimated the nAb titers from the serological samples against the SARS-CoV-2 D614G strain, as well as the Delta and the Omicron BA.1, BA.2, and BA.5 sublineages, approximately four to six months after the administration of the booster dose.

Furthermore, the team examined the evolution of cross-neutralization in the serum samples for up to 16 months after the initial vaccination. Immunoglobulin G (IgG) levels as well as nAb titers were represented at various time points post the second and third vaccinations and after the incidence of Omicron BA.1 or BA.1 breakthrough infection. Subsequently, the team estimated the nAb titers of six vaccines and three persons having no history of breakthrough COVID-19 infection. Moreover, the impact of vaccination, as well as breakthrough infections on different antibody responses, were also assessed by measuring anti-spike(S) IgG levels and cross-neutralizing activity in the participants.  

Results

The study results showed that among the 27 healthcare workers assessed, 11 reported paucisymptomatic breakthrough COVID-19 infection approximately 60 to 178 days after the booster vaccination. Polymerase chain reaction (PCR) confirmed that the breakthrough infections were caused by the SARS-CoV-2 Omicron variant.

The team noted that the Omicron subvariants exhibited substantial immune evasion as compared to the D614G strain and the Delta variant. Among the Omicron infections, BA.5 neutralization was insignificant and was found to be reduced by 2.5 and 1.7 times in comparison to BA.1 and BA.2, respectively. Hence, breakthrough BA.1 or BA.2 infections increased Omicron-specific neutralizing antibody titers which were notably lesser against BA.5.

Furthermore, the team observed peak anti-spike IgG levels one-month post-second vaccination which waned over the following 10 months. A booster vaccination elicited higher IgG peak values as compared to those after the second vaccine dose. Moreover, the regression model showed that IgG concentrations were undetectable almost 1.91 years after the second dose and 1.95 years after the third dose. Notably, breakthrough infection boosted IgG levels without any significant reduction for up to five months.

The team also observed variations in the neutralization profiles of the variants. No neutralization was detected against Omicron BA.1, BA.2, and BA.5 following the second dose while D614G and Delta exhibited substantial neutralization. After the administration of the booster vaccine, serum samples neutralized all the variants tested, while differences were noted in the peak values and the durations of neutralization. The nAb titers were undetectable against the D614G strain after 11.5 months, the Delta variant and BA.1 subvariant after eight months, and the BA.5 subvariant after 5.5 months.     

The team remarked that breakthrough Omicron infections were reported two to five months after the booster dose vaccination and resulted in an improvement in nAb titers and anti-S IgG levels. However, non-infected persons showed a consistent reduction in nAb titers over time. Overall, this suggested that individuals vaccinated with the booster dose displayed shorter neutralization effectiveness against BA.5.

Furthermore, it was observed that concentrations of anti-SARS-CoV-2 IgA and IgG elicited by BNT162b2 vaccination were relatively low, which suggested the absence of strong local immunity. Moreover, breakthrough infections induced a moderate increase of 2.2 times in IgG levels while a 12 times increase was observed in IgA levels. Individuals vaccinated with the booster dose displayed no neutralization activity against Omicron or Delta. Notably, the neutralization activity was substantially higher against BA.1, BA.2, and D614G than against BA.5 and Delta. Additionally, Omicron breakthrough infection - not vaccination, elicited a local nAb response in the host at the time of viral entry.

Conclusion

Overall, the study findings showed that immunity induced by breakthrough COVID-19 infections resulted in higher neutralization activity against SARS-CoV-2 variants than by COVID-19 vaccination.          

*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:
  • Delphine Planas, Isabelle Staropoli, Françoise Porot, Florence Guivel-Benhassine, Lynda Handala, Mathieu Prot, William-Henry Bolland, Julien Puech, Hélène Péré, David Veyer, Aymeric Sève, Etienne-Simon-Lorière, Timothée Bruel, Thierry Prazuck, Karl Stefic, Laurent Hocqueloux, Olivier Schwartz. (2022). Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without Omicron breakthrough infection. medRxivdoi: https://doi.org/10.1101/2022.07.22.22277885 https://www.medrxiv.org/content/10.1101/2022.07.22.22277885v1
Bhavana Kunkalikar

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Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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