Three doses of Novavax vaccine are effective against Omicron subvariants

A recent article was published in bioRxiv * Prepress server reported that the coronavirus disease 2019 (COVID-19) vaccine NVX-CoV2373 results in strong neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron.

Stady: Novavax NVX-COV2373 effectively neutralizes the Omicron sub-lineages. Image Credit: Studio Roux / Shutterstock.com

background

The SARS-CoV-2 Omicron variant of concern (VOC) and its sub variants BA.4, BA.5, BA.2, and BA.2.12.1 possess several spike (S) mutations responsible for the high level of resistance observed against neutralization induced by The COVID-19 vaccine, regardless of the vaccine platform. Similarly, individuals with a prior history of COVID-19 also display a low equivalence titer against several Omicron subvariants.

However, booster vaccination has been shown to improve the ability to neutralize omicron, especially with messenger ribonucleic acid (mRNA) vaccines.

NVX-CoV2373 is a protein nanoparticle vaccine for COVID-19 that has been particularly useful in countries with limited cold chain requirements. NVX-CoV2373 is listed in the World Health Organization (WHO) emergency use category for COVID-19 vaccines and has been authorized for use by the European Medicines Agency.

about studying

In the current study, researchers report neutralization of SARS-CoV-2 titers, including those against several substrains of Omicron, after double and triple vaccination with NVX-CoV2373 vaccine. To this end, they evaluated how a third dose affected the ability of serum of NVX-CoV2373 vaccine recipients to neutralize SARS-CoV-2 and these variants.

Neutralization of SARS-CoV-2 progenitor strains D614G, Omicron BA.4, BA.1, BA.5, and Beta was evaluated by sera of 29 and 48 of NVX-CoV2373 vaccine recipients after completion of two and three. Vaccine dose regimens, respectively. The Omicron BA.4, BA.5, and BA.1 equivalence were also evaluated after multiple doses of mRNA, adenovirus, and protein-based COVID-19 vaccines.

Results

Mean geometric titers (GMTs), measured 14 days after vaccination with two doses of NVX-CoV2373, peaked against the SARS-CoV-2 D614G variant with 1,401 GMT. GMT then dropped to 34, 47 and 173 against Omicron BA.1 and Omicron BA.4/BA.5 and Beta respectively.

Notably, the Omicron BA.4/BA.5 and BA.1 subvariants were impermeable to neutralization with titers below the detection range of the assay of 72% after two doses of NVX-CoV2373 vaccine.

Neutralization of the antibody response with a titer exceeding 1:200 versus the Omicron BA.1 and Beta variants was noticeable 1 month after the third dose of NVX-CoV2373 in 47 of 48 samples. In addition, the neutralizing antibody titer against SARS-CoV-2 strain D614G was increased to 10,862 GMT.

Moreover, a third dose of NVX-CoV2373 improved titers against Omicron BA.1, BA.4/BA.5 and Beta, with 1,197, 582, and 1,733 BST, respectively. However, these titers were six to eight times lower than those of the D614G.

After three doses of NVX42 CoV2373, all but one sample had variable titers of Omicron above 50% of the protective levels.

Neutralization of SARS-CoV-2 variants by NVX-CoV2373 vaccine plasma.  Neutralization of D164G, Beta, Omicron BA.1 and Omicron BA.4/BA.5 progenitor viruses by NVX-CoV2373 vaccine plasma after 2 (grey) or 3 (teal) doses.  Mean geometric titers (GMT) of each virus are shown above the individual points, and the percentage of samples in which no neutralization was observed (red) is indicated in the pie charts.  The number of tested vaccine samples was indicated and p-values ​​were calculated using the Mann-Whitney t-test for non-parametric data with p <0،001 لـ D614G و Beta و Omicron BA.1 و Omicron BA.4 / BA.5.  يشير الخط المتقطع إلى مستوى التعادل عند 20.2 ٪ من متوسط ​​مستوى النقاهة (ID50 = 200) ، والذي يوفر حماية تقديرية بنسبة 50 ٪ ضد عدوى SARS-CoV-2 التي يمكن اكتشافها وفقًا لتحليل أجراه خوري وآخرون.  تم استخدام العينات في بداية تخفيف 1 من 20 (حد الاكتشاف) مع سبعة تخفيفات 3 أضعاف لإنشاء سلسلة معايرة. Neutralization of SARS-CoV-2 variants by NVX-CoV2373 vaccine plasma. Neutralization of D164G, Beta, Omicron BA.1 and Omicron BA.4/BA.5 progenitor viruses by NVX-CoV2373 vaccine plasma after 2 (grey) or 3 (teal) doses. Mean geometric titers (GMT) of each virus are shown above the individual points, and the percentage of samples in which no neutralization was observed (red) is indicated in the pie charts. The number of tested vaccine samples was indicated and p-values ​​were calculated using a Mann-Whitney t-test for non-parametric data with p < 0.001 for D614G, Beta, Omicron BA.1 and Omicron BA.4/BA.5. The dashed line indicates the break-even level at 20.2% of the mean convalescent level (ID50 = 200), which provides an estimated 50% protection against detectable SARS-CoV-2 infection according to an analysis by Khoury. and others15th. Samples were used at the start of a 1 out of 20 dilution (the limit of detection) with seven 3-fold dilutions to create a calibration series.

Two doses of Johnson & Johnson AD26.COV2.S vaccine induced 14- and 10-fold lower GMT responses against the Omicron BA.1 variant compared to three doses of NVX-CoV2373 and Pfizer-BioNTech mRNA BNT162b2, respectively. Similarly, the AD26.COV2.S vaccine stimulated 11- and 12-fold lower GMT targeting BA.4/BA.5 than three doses of NVX-CoV2373 and BNT162b2 vaccines, respectively.

Only 13-38% of AD26.COV2.S samples neutralized Omicron BA.4/BA.5 and BA.1 at titers above 200. This was similar to most plasma samples showing this level of protection from three NVX-CoV2373 dose recipients. BNT162b2 vaccine.

Due to lower GMT for all three booster vaccine regimens against BA.4/BA.5, 91% of NVX-CoV2373 and 83% of BNT162b2 samples were neutralized compared to 13% of AD26.COV.S samples that were neutralized BA.5/ BA. 4 counters above 1:200 threshold. GMTs targeting BA.4/BA.5 from plasma immunized with three doses of NVX-CoV2373 were similar to BNT162b2, while BA.1 neutralizing titers were superior in the NVX-COV2373 group.

Neutralization of Omicron BA.1 and BA.4/BA.5 by vaccine-boosted plasma.  Neutralization of Omicron BA.1 and BA.4/BA.5 by vaccine plasma after 2 doses of AD26.COV2S or 3 doses of BNT162b2 or NVX-CoV2373 vaccines.  The number of doses, the number of samples, and the date of sample collection after reinforcement are indicated for each group.  Geometric mean (GMT) titers of each virus are shown over individual points, and P values ​​were calculated using two-way ANOVA with p <0،001 لـ AD26CoV2.S مقابل NXV-CoV2373 و p = 0،0011 لـ NVX-CoV2373 BA.1 مقابل BA.4 / BA.5).  يشير الخط المتقطع إلى مستوى التعادل عند 20،2 ٪ من متوسط ​​مستوى النقاهة (ID50 = 200) ، والذي يوفر حماية تقديرية بنسبة 50 ٪ ضد عدوى SARS-CoV-2 التي يمكن اكتشافها وفقًا لتحليل أجراه خوري وآخرون. Neutralization of Omicron BA.1 and BA.4/BA.5 by vaccine-boosted plasma. Neutralization of Omicron BA.1 and BA.4/BA.5 by vaccine plasma after 2 doses of AD26.COV2S or 3 doses of BNT162b2 or NVX-CoV2373 vaccines. The number of doses, the number of samples, and the date of sample collection after reinforcement are indicated for each group. Geometric mean titers (GMT) of each virus are shown over individual points, and P values ​​were calculated using two-way ANOVA with p < 0.001 for AD26CoV2.S versus NXV-CoV2373 and p = 0.0011 for NVX-CoV2373 BA. 1 vs. BA.4 / BA.5). The dashed line indicates the break-even level at 20.2% of the mean convalescent level (ID50 = 200), which provides an estimated 50% protection against detectable SARS-CoV-2 infection according to an analysis by Khoury. and others The.

Conclusions

The results of the current study demonstrate that three doses of the COVID-19 NVX-CoV2373 vaccine significantly improved the neutralization of SARS-CoV-2 Omicron BA.4/BA.5 and BA.1 subvariants with responses similar to those achieved with three doses of mRNA vaccine.

Notably, enhanced bound antibody levels were detected six months after two doses of NVX-CoV2373. Thus, future studies should evaluate NVXCoV2373 neutralization at later time points, as the longevity of different vaccine platforms can vary.

As the SARS-CoV-2 Omicron BA.4 variant has become the dominant circulating strain in multiple regions, the study results emphasize the potential use of NVX-CoV2373 vaccine as a booster dose, especially in areas with limited resources.

*Important note

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

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