Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Tuekprakhon, Aekkachai; Huo, Jiandong; Nutalai, Rungtiwa; Dijokaite-Guraliuc, Aiste; Zhou, Daming; Ginn, H.; Selvaraj, Muneeswaran; Liu, Chang; Mentzer, Alexander J.; Supasa, Piyada; Duyvesteyn, H.M.E.; Das, Raksha; Skelly, Donal; Ritter, Thomas G.; Amini, Ali; Bibi, Sagida; Adele, Sandra; Johnson, Síle A.; Constantinides, Bede; Webster, Hermione J.; Temperton, Nigel; Klenerman, Paul; Barnes, Eleanor; Dunachie, Susanna; Crook, Derrick W.; Pollard, Andrew J.; Lambe, Teresa; Goulder, Philip; Paterson, Neil G.; Williams, Mark A.; Hall, David R.; Fry, Elizabeth E.; Mongkolsapaya, Juthathip; Ren, Jingshan; Stuart, David I.; Screaton, Gavin; Conlon, Christopher P.; Deeks, Alexandra; Frater, John; Frending, Lisa; Gardiner, Siobhan; Jämsén, Anni; Jeffery, Katie; Malone, Tom; Phillips, Eloise; Rothwell, Lucy; Stafford, Lizzie

doi:10.1016/j.cell.2022.06.005

Cited by 585 publications

(622 citation statements)

References 58 publications

Supporting

Mentioning

568

Contrasting

Unclassified

Order By: Relevance

“…Laboratory studies [2][3][4][5][6] consistently suggest that antibodies triggered by vaccination are less effective at blocking BA.4 and BA.5 than they are at blocking earlier Omicron strains, including BA.1 and BA.2. This could leave even vaccinated and boosted people vulnerable to multiple Omicron infections, scientists say.…”

Section: How Well Do Vaccines Work Against the Variants?mentioning

confidence: 99%

What Omicron’s BA.4 and BA.5 variants mean for the pandemic

Callaway¹

2022

Nature

120

119

View full text Add to dashboard Cite

Section: How Well Do Vaccines Work Against the Variants?mentioning

confidence: 99%

What Omicron’s BA.4 and BA.5 variants mean for the pandemic

Callaway¹

2022

Nature

120

119

View full text Add to dashboard Cite

“…BA.5 became predominant worldwide by mid-2022 and was responsible for a surge of contaminations in many countries 16,17 . The neutralizing activity of sera from COVID-19 vaccine recipients is reduced against BA.5 by about 3-5 fold compared to BA.1 and BA.2 11,[18][19][20][21][22] . Little is known about real-world vaccine efficacy against BA.5 infections, in individuals that were or were not previously infected with BA.1 or BA.2.…”

mentioning

confidence: 99%

Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without Omicron breakthrough infection

Planas

Staropoli

Porrot

et al. 2022

Preprint

View full text Add to dashboard Cite

Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, that displays enhanced antibody escape properties. Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 16 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta and Omicron BA.1, BA.2, BA.5 variants in 291 sera and 35 nasal swabs from 27 individuals. Upon vaccination, serum Nab titers were reduced by 10, 15 and 25 fold for BA.1, BA.2 and BA.5, respectively, compared with D614G. The duration of neutralization was markedly shortened, from an estimated period of 11.5 months post-boost with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 4 or 5 months. In nasal swabs, infection, but not vaccination, triggered a strong IgA response and a detectable Omicron neutralizing activity. Thus, BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants.

show abstract

“…Compared to BA.2 spike, BA.2.12.1 contains two additional mutations (L452Q and S704L) while BA. 4 and BA.5 spikes are identical and have 4 constant alterations (Del69-70, L452R, F486V, R493Q) plus one mutation (N658S) seen in earlier sequences (Fig. 1a-1b).…”

mentioning

confidence: 78%

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron subvariants BA.2, BA.2.12.1 and BA.5

Fang

Chen

2022

Preprint

View full text Add to dashboard Cite

As the immune protection conferred by first booster shot wanes over time and new Omicron subvariant emerges with stronger immune evasion, the need for variant-adapted COVID vaccine booster is increasingly imminent. However, the rapid replacement of dominant Omicron subvariants (from BA.1 to BA.2, then BA.2.12.1 and now BA.4/5) poses a great challenge to update COVID vaccine targeting the fast-evolving variants while maintaining potency against existing variants. It is a crucial question to ask which variant-based antigen(s) to use in the next generation COVID vaccine to elicit potent and broad response to past, present, and potential rising variants. Bivalent vaccine candidates have been under active clinical testing such as Modern mRNA-1273.214. In this study, we generate a Delta + BA.2 bivalent mRNA vaccine candidate and tested in animals. We compare the antibody response elicited by ancestral (wild type, WT), Delta, BA.2 spike based monovalent or Delta & BA.2 bivalent mRNA boosters against Omicron BA.2, BA.2.12.1 and BA.4/5 subvariants. In mice pre-immunized with two doses of WT lipid nanoparticle mRNA (LNP-mRNA), all three monovalent and one bivalent boosters elevated Omicron neutralizing antibody titers to various degree. The boosting effect of Delta and BA.2 specific monovalent or bivalent LNP-mRNAs is universally higher than that of WT LNP-mRNA, which modestly increased antibody titer in neutralization assays of Omicron BA.5, BA.2.12.1 and BA.2. The Delta & BA.2 bivalent LNP-mRNA showed better performance of titer boosting than either monovalent counterparts, which is especially evident in neutralization of Omicron BA.4 or BA.5. Interestingly compared to the neutralizing titers of BA.2 and BA.2.12.1 pseudovirus, BA.2 monovalent but not Delta & BA.2 bivalent booster suffered a significant loss of BA.4/5 neutralizing titer, indicative of broader activity of bivalent booster and strong neutralization evasion of Omicron BA.4 or BA.5 even in the BA.2 mRNA vaccinated individuals. These data provide evaluation of WT, Delta, BA.2 monovalent and bivalent boosters antibody potency against Omicron BA.2, BA.2.12.1 and BA.4/5 subvariants.

show abstract

Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Cited by 585 publications

References 58 publications

What Omicron’s BA.4 and BA.5 variants mean for the pandemic

What Omicron’s BA.4 and BA.5 variants mean for the pandemic

Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without Omicron breakthrough infection

Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron subvariants BA.2, BA.2.12.1 and BA.5

Contact Info

Product

Resources

About