Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination

Tauzin, Alexandra; Benlarbi, Mehdi; Medjahed, Halima; Grégoire, Yves; Perreault, Josée; Gendron‐Lepage, Gabrielle; Gokool, Laurie; Morrisseau, Chantal; Arlotto, Pascale; Tremblay, Cécile; Kaufmann, Daniel E.; Martel-Laferrière, Valérie; Levade, Inès; Côté, Marceline; Serres, Gaston De; Bazin, Renée; Finzi, Andrés

doi:10.3390/vaccines11020242

Cited by 5 publications

(15 citation statements)

References 34 publications

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“…In the general population, humoral responses are efficiently generated after the SARS-CoV-2 mRNA vaccine and increased after vaccinal boosts [ 16 , 29 , 42 ]. These responses are important since the neutralizing activity of antibodies elicited after vaccination is central to protect and predict the immune response to the SARS-CoV-2 infection [ 33 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

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Humoral Responses Elicited by SARS-CoV-2 mRNA Vaccine in People Living with HIV

Marchitto,

Chatterjee,

Ding

et al. 2023

Viruses

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While mRNA SARS-CoV-2 vaccination elicits strong humoral responses in the general population, humoral responses in people living with HIV (PLWH) remain to be clarified. Here, we conducted a longitudinal study of vaccine immunogenicity elicited after two and three doses of mRNA SARS-CoV-2 vaccine in PLWH stratified by their CD4 count. We measured the capacity of the antibodies elicited by vaccination to bind the Spike glycoprotein of different variants of concern (VOCs). We also evaluated the Fc-mediated effector functions of these antibodies by measuring their ability to eliminate CEM.NKr cells stably expressing SARS-CoV-2 Spikes. Finally, we measured the relative capacity of the antibodies to neutralize authentic SARS-CoV-2 virus after the third dose of mRNA vaccine. We found that after two doses of SARS-CoV-2 mRNA vaccine, PLWH with a CD4 count < 250/mm3 had lower levels of anti-RBD IgG antibodies compared to PLWH with a CD4 count > 250/mm3 (p < 0.05). A third dose increased these levels and importantly, no major differences were observed in their capacity to mediate Fc-effector functions and neutralize authentic SARS-CoV-2. Overall, our work demonstrates the importance of mRNA vaccine boosting in immuno-compromised individuals presenting low levels of CD4.

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Section: Discussionmentioning

confidence: 99%

“…With the increased rate of VOCs, several studies have shown decreased neutralizing capacities of antibodies elicited after mRNA vaccination against the different Spikes [ 15 , 42 , 46 ]. However, antibodies’ Fc-effector functions, such as ADCC, are part of the immune response and help clear the viral infection [ 25 , 40 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Humoral Responses Elicited by SARS-CoV-2 mRNA Vaccine in People Living with HIV

Marchitto,

Chatterjee,

Ding

et al. 2023

Viruses

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“…Most studies, including this one, showed that the new variants have different degrees of resistance to neutralization induced by vaccination. However, although there is an important circulation of the variants in the population, no increase in the number of severe forms of COVID-19 were observed, indicating that the vaccines remain effective [ 16 , 20 , 29 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…The plasmids encoding the SARS-CoV-2 D614G, BA.1, BA.4/5, and BQ.1.1 Spike variants were previously described [ 10 , 20 , 33 ]. The pNL4.3 R-E-Luc plasmid was obtained from the NIH AIDS Reagent Program (cat# 3418).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, to increase the efficacy of vaccines against the new variants, bivalent vaccines, expressing both the ancestral and an Omicron variant Spike (BA.1 or BA.4/5), have been developed by Pfizer and Moderna. However, several studies have shown that these new bivalent vaccines only weakly increase humoral responses against the new subvariants compared to the monovalent vaccine, and poor neutralizing responses against Omicron variants were still observed after vaccination with the bivalent mRNA vaccine [ 17 , 20 , 21 , 22 ]. Also, due to the high transmissibility of the Omicron subvariants and low humoral responses, the vaccine provides weak protection against infection [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Humoral Responses Elicited after a Fifth Dose of SARS-CoV-2 mRNA Bivalent Vaccine

Tauzin,

Beaudoin-Bussières,

Benlarbi

et al. 2023

Viruses

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While an important part of the world’s population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize several Omicron subvariants, including BQ.1.1, XBB, XBB.1.5, FD.1.1, and CH.1.1. However, Fc-effector functions remain strong and stable over time against new variants, which may partially explain why vaccines continue to be effective. We also observe that donors who have been recently infected have stronger antibody functional activities, including neutralization and Fc-effector functions, supporting the observations that hybrid immunity leads to better humoral responses.

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Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission

Benlarbi,

Ding,

Bélanger

et al. 2024

mBio

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The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring of its subvariants. Omicron subvariants are responsible for the vast majority of SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% of circulating strains as of January 2024. To better understand parameters involved in viral transmission, we characterized the functional properties of Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, BA.2.86 and JN.1. We tested their capacity to evade plasma-mediated recognition and neutralization, binding to angiotensin-converting enzyme 2 (ACE2), their susceptibility to cold inactivation, Spike processing, as well as the impact of temperature on Spike-ACE2 interaction. We found that compared to the early wild-type (D614G) strain, most Omicron subvariants' Spike glycoproteins evolved to escape recognition and neutralization by plasma from individuals who received a fifth dose of bivalent (BA.1 or BA.4/5) mRNA vaccine and improve ACE2 binding, particularly at low temperatures. Moreover, BA.2.86 had the best affinity for ACE2 at all temperatures tested. We found that Omicron subvariants’ Spike processing is associated with their susceptibility to cold inactivation. Intriguingly, we found that Spike-ACE2 binding at low temperature was significantly associated with growth rates of Omicron subvariants in humans. Overall, we report that Spikes from newly emerged Omicron subvariants are relatively more stable and resistant to plasma-mediated neutralization, present improved affinity for ACE2 which is associated, particularly at low temperatures, with their growth rates. IMPORTANCE The persistent evolution of SARS-CoV-2 gave rise to a wide range of variants harboring new mutations in their Spike glycoproteins. Several factors have been associated with viral transmission and fitness such as plasma-neutralization escape and ACE2 interaction. To better understand whether additional factors could be of importance in SARS-CoV-2 variants’ transmission, we characterize the functional properties of Spike glycoproteins from several Omicron subvariants. We found that the Spike glycoprotein of Omicron subvariants presents an improved escape from plasma-mediated recognition and neutralization, Spike processing, and ACE2 binding which was further improved at low temperature. Intriguingly, Spike-ACE2 interaction at low temperature is strongly associated with viral growth rate, as such, low temperatures could represent another parameter affecting viral transmission.

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Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination

Cited by 5 publications

References 34 publications

Humoral Responses Elicited by SARS-CoV-2 mRNA Vaccine in People Living with HIV

Humoral Responses Elicited by SARS-CoV-2 mRNA Vaccine in People Living with HIV

Humoral Responses Elicited after a Fifth Dose of SARS-CoV-2 mRNA Bivalent Vaccine

Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission

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