Three doses of Novavax vaccine are effective against Omicron subvariants

A recently published article bioRxiv* The preprint server reports that the coronavirus disease 2019 (COVID-19) vaccine NVX-CoV2373 exerts potent neutralization against the coronavirus 2 (SARS-CoV-2) Omicron subvariants.

The research: Novavax NVX-COV2373 provides potent neutralization of Omicron sub-lines. Photo credit: Studio Roux / Shutterstock.com

Background

The Omicron variant (VOC) of SARS-CoV-2 and its subvariants BA.4, BA.5, BA.2 and BA.2.12.1 have many spike (S) mutations that confer high levels of resistance. was observed against neutralization induced by the COVID-19 vaccine, regardless of the vaccine platform. Similarly, individuals with a prior history of COVID-19 also have reduced neutralizing titers against several Omicron subvariants.

Nevertheless, booster vaccination improves Omicron neutralization capacity, particularly with reporter ribonucleic acid (mRNA) vaccines.

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

About reading

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

Neutralization of SARS-CoV-2 parental D614G, Omicron BA.4, BA.1, BA.5 and Beta strains with sera from 29 and 48 NVX-CoV2373 vaccine recipients was assessed after completion of two and three replicates. – doses of the vaccine, respectively. Neutralization of Omicron BA.4, BA.5, and BA.1 was also evaluated after multiple doses of mRNA, adenoviral, and protein-based COVID-19 vaccines.

Research results

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

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

In 47 of 48 samples, neutralizing antibody responses with titers of 1:200 against Omicron BA.1 and Beta variants were observed more than one month after the third NVX-CoV2373 dose. In addition, neutralizing antibody titers against the SARS-CoV-2 D614G strain were increased to 10,862 GMT.

Furthermore, the third NVX-CoV2373 dose resulted in improved titers against Omicron BA.1, BA.4/BA.5, and Beta, with GMTs of 1.197, 582, and 1.733, respectively. However, these titers were six to eight times lower than against D614G.

After three NVX42 CoV2373 doses, all but one sample had Omicron subvariant titers greater than 50% protection.

Neutralization of SARS-CoV-2 variants by NVX-CoV2373 vaccine plasma.  Neutralization of ancestral D164G, Beta, Omicron BA.1, and Omicron BA.4/BA.5 pseudoviruses by NVX-CoV2373 vaccine plasma after 2 (grey) or 3 (old) doses.  Geometric mean titers (GMT) for each virus are shown above the individual dots, and pie charts show the percentage of samples showing no neutralization (red).  The number of vaccine samples tested is shown and the p values ​​are for D614G, Beta, Omicron BA.1 and Omicron BA.4/BA.5. < 0,001 менен параметрлик эмес маалыматтар үчүн Mann-Whitney t-test аркылуу эсептелген.  Үзүктүү сызык нейтралдаштыруу деңгээлин орточо калыбына келтирүү деңгээлинин 20,2% көрсөтөт (ID50 = 200), бул Khoury жана башкалар тарабынан талдоо боюнча аныкталган SARS-CoV-2 инфекциясынан болжолдуу 50% коргоону камсыз кылат15.  Үлгүлөр титрлөө сериясын түзүү үчүн 20дан 1 (аныктоо чеги) баштапкы суюлтууда 3 эселенген жети суюлтууда колдонулган. Neutralization of SARS-CoV-2 variants by NVX-CoV2373 vaccine plasma. Neutralization of ancestral D164G, Beta, Omicron BA.1, and Omicron BA.4/BA.5 pseudoviruses by NVX-CoV2373 vaccine plasma after 2 (grey) or 3 (old) doses. Geometric mean titers (GMT) for each virus are shown above the individual dots, and pie charts show the percentage of samples showing no neutralization (red). The number of vaccine samples tested is indicated and p values ​​were calculated using the 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 neutralization level at 20.2% of the average recovery level (ID)50 = 200), which provides an estimated 50% protection against SARS-CoV-2 infection as determined by Khoury’s analysis. etc.15. Samples were used in seven 3-fold dilutions at an initial dilution of 1 in 20 (limit of detection) to make a titration series.

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

Only 13-38% of AD26.COV2.S samples neutralized Omicron BA.4/BA.5 and BA.1 above 200 titers. This is comparable to the majority of plasma samples showing this level of protection against three NVX-CoV2373. and recipients of the BNT162b2 vaccine dose.

Considering that GMT was reduced for all three vaccine regimens boosted against BA.4/BA.5, 91% of NVX-CoV2373 samples and 13% of BNT162b2 samples compared to BA.5/BA neutralized AD26.COV.S samples. 4 at titers above the 1:200 threshold. GMTs targeting BA.4/BA.5 of three-dose NVX-CoV2373 vaccinated plasma were similar to BNT162b2, whereas BA.1 neutralization titers were higher in the NVX-COV2373 cohort.

Neutralization of Omicron BA.1 and BA.4/BA.5 with boosted vaccine plasma.  Neutralization with Omicron BA.1 and BA.4/BA.5 vaccine plasma after 2 doses of AD26.COV2S or 3 doses of BNT162b2 or NVX-CoV2373 vaccine.  Number of doses, number of samples, and date of sampling after boost for each group are shown.  Geometric mean titers (GMT) for each virus are shown above individual dots, p values ​​for NXV-CoV2373 versus AD26CoV2.S < 0,001 жана NVX-CoV2373 BA.1 үчүн p = 0,0011 менен эки тараптуу ANOVA аркылуу эсептелген. каршы BA.4/BA.5).  Үзүктүү сызык нейтралдаштыруу деңгээлин орточо калыбына келтирүү деңгээлинин 20,2% көрсөтөт (ID50 = 200), бул Khoury жана башкалар тарабынан талдоо боюнча аныкталган SARS-CoV-2 инфекциясынан болжолдуу 50% коргоону камсыз кылат15. Neutralization of Omicron BA.1 and BA.4/BA.5 with boosted vaccine plasma. Neutralization with Omicron BA.1 and BA.4/BA.5 vaccine plasma after 2 doses of AD26.COV2S or 3 doses of BNT162b2 or NVX-CoV2373 vaccine. Number of doses, number of samples, and date of sampling after boost for each group are shown. Geometric mean titers (GMT) for each virus are shown above individual dots, P values ​​were calculated by two-way ANOVA with p < 0.001 for NXV-CoV2373 vs. AD26CoV2.S and p = 0.0011 for NVX-CoV2373 BA.1. vs. BA.4/BA.5). The dashed line indicates the neutralization level at 20.2% of the average recovery level (ID)50 = 200), which provides an estimated 50% protection against SARS-CoV-2 infection as determined by Khoury’s analysis. etc there.

Conclusions

The results of the current study show 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 comparable to those achieved. with three mRNA vaccine doses.

Notably, enhanced levels of binding antibodies were detected six months after two doses of NVX-CoV2373. Thus, future studies should evaluate neutralization of NVXCoV2373 at later times, as the duration of different vaccine platforms may vary.

As the SARS-CoV-2 Omicron BA.4 variant has become the dominant circulating strain in several regions, the study findings highlight the use of NVX-CoV2373 as a vaccination booster, especially in resource-limited regions.

*Important note

bioRxiv publishes non-peer-reviewed preliminary scientific reports and therefore should not be considered as conclusive, clinical practice/health-related behavior guidance, or as prescribed information.

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