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Sturdy neutralizing response towards Omicron after heterologous vaccine boosting

The at the moment dominant circulating Omicron variant of the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of plenty of mutations, a few of which have conferred improved transmissibility and immune evasive properties to this pressure. This pathogenically enhanced SARS-CoV-2 variant has led to an elevated charge of vaccine breakthrough infections.

Research: Speedy decline in vaccine-boosted neutralizing antibodies towards SARS-CoV-2 Omicron variant. Picture Credit score: Marco Lazzarini /


A substantial quantity of analysis has confirmed that the first two-dose coronavirus illness 2019 (COVID-19) vaccination collection produces a poor immune response towards the Omicron variant and {that a} third vaccine dose or booster is crucial to confer significant safety towards this variant. Regardless of these observations, researchers are nonetheless seeking to perceive the extent of safety conferred by neutralizing antibodies towards the Omicron variant.

In a current Cell Experiences Drugs* preprint, researchers discovered that neutralizing antibodies towards the Omicron variant which were generated from the vaccine booster exhibit a big decline inside three months of the booster dose. Nonetheless, the neutralizing potential of those antibodies towards the prototypic D614G SARS-CoV-2 pressure stays strong.

Whereas testing the potential impression of boosting with a heterologous vaccine, the researchers discovered the Johnson & Johnson Ad26.COV2.S vaccine supplies higher safety if given as a first-rate vaccine or booster dose with a heterologous messenger ribonucleic acid (mRNA) vaccine as in comparison with when given as a homologous vaccine.

Additional, in evaluating the virus neutralization response towards the BA.1, BA.2 & BA.3 Omicron sublineages, the researchers of the present examine noticed an identical response induced towards all three by homologous mRNA vaccine booster.

In regards to the examine

Within the present examine, the researchers assessed the impression of homologous and heterologous primary-booster vaccine dose mixtures on 20 people per mixture, of which included:

  • Homologous 50 μg main and booster mRNA1273 (Moderna)
  • Homologous 100 μg main and booster mRNA1273 (Moderna)
  • Homologous main and booster BNT162b2 (Pfizer-BioNTech)
  • Homologous main and booster Ad26.COV2.S (Johnson & Johnson)
  • Heterologous: Ad26.COV2.S main and BNT162b2 booster
  • Heterologous: BNT162b2 main and Ad26.COV2.S booster

Neutralizing antibody titers were assayed using pseudovirus neutralization assay (PsVNA) and live virus focus reduction neutralization (FRNT) assay.

Study findings

Baseline PsVNA titers that were obtained just before receiving the booster dose against the prototypic D614G variant were observed in 85-100% of the individuals with geometric mean titers (GMTs) in the range of 35-343 from all tested groups. However, these titers were comparatively low against the Omicron variant, with GMTs within the range of seven and 25 in 20-90% of all study participants.

Post-booster titers on day 29 increased to more than 1,000 for the D614G variant and more than 250 for the Omicron variant from all groups except those who received homologous Ad26.COV2.S prime and booster doses. Day 29 post-booster neutralizing titers were 2.3- to 7.5-fold lower for the Omicron variant as compared to the D614G variant across all the vaccine groups.

In all cases, the boosted PsVNA titers against the D614G variant were more durable than those against Omicron, perhaps reflecting greater maturation of humoral immunity between closely matched vaccine and variant spike proteins.”

The team also found similar antibody titers produced against all three Omicron sublineages on day 29 when tested on a subset from homologous mRNA-1273 boosting.

Between day 29 to day 91 post-booster, the researchers observed a rapid decline of 4.1- to 6.0-fold in neutralizing GMTs against Omicron, but only up to 1.8-fold decline for the D614G variant. Notably, from day 29 to 91 in the two Ad26.COV2.S-boosted groups, neutralizing GMT against D614G variant, but not Omicron, remained either constant or slightly improved. This indicates that the Ad26.COV2.S vaccine was responsible for sustained durability of virus-neutralizing responses as compared to the mRNA vaccines.

Homologous boosting with Ad26.COV2.S resulted in low PsVNA titers against the Omicron variant, while titers were high when Ad26.COV2.S was used as a heterologous prime or booster with an mRNA vaccine.

These data support that homologous mRNA and heterologous boost combinations will increase humoral immunity to Omicron as a strategy to mitigate risk from this and possibly future variants.”

*Important notice

Sneak Peek/ Cell Press 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.

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