Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Munro, Alasdair; Feng, Luzhao; Janani, Leila; Cornelius, Victoria; Aley, Parvinder K.; Babbage, Gavin; Baxter, David; Bula, Marcin; Cathie, Katrina; Chatterjee, Krishna; Dodd, Kate; Qureshi, Ehsaan; Goodman, Anna; Green, Christopher; Harndahl, Linda; Haughney, John; Hicks, Alexander; Klaauw, Agatha A. van der; Kanji, Nasir; Llewelyn, Martin; Minassian, Angela M.; Mughal, Mehmood; Mujadidi, Yama F; Holliday, Kyra; Osanlou, Orod; Osanlou, Rostam; Owens, Daniel R; Pacurar, Mihaela; Palfreeman, Adrian; Pan, Daniel; Regan, Karen; Saich, Stephen; Bawa, Tanveer; Saralaya, Dinesh; Sharma, Sunil; Sheridan, Ray; Thomson, Emma C.; Todd, Shirley; Twelves, Chris; Read, Robert C.; Ramsay, Mary; Andrews, Nick; Lambe, Teresa; Nguyen‐Van‐Tam, Jonathan S; Snape, Matthew D; Liu, Xinxue; Faust, Saul N; Enever, Yvanne; Libri, Vincenzo; McGregor, Alastair; Moore, Patrick; Rampling, Tommy; Maallah, Mina; Charlton, Sue; Hallis, Bassam; Riordan, Andrew; Ustianowski, Andrew; Rogers, Chris; Katechia, Kashyap; Cooper, Alexandra; Freedman, Andrew; Hughes, Rachel; Grundy, Lynne; Jones, L.; Harrison, E.; Snashall, Emma; Mallon, Lewis; Burton, Katharine; Storton, Kim; Munusamy, Malathi; Tandy, Bridget; Egbo, Akamino; Cox, S. F. J.; Ahmed, Nabeela Nazir; Shenoy, Anil; Bousfield, Rachel; Wixted, Donna; Gutteridge, Helen; Mansfield, Becky; Herbert, Christopher J.; Murira, Jennifer; Calderwood, J.H.; Bourg, Dominique; Brandon, Jacqueline; Tulloch, Hayley; Colquhoun, Suzie; Thorp, H. Holden; Radford, Helen; Evans, Julie; Baker, H. M.; Thorpe, Jeanette; Batham, Sally; Hailstone, Jessica; Phillips, Rachael V.; Kumar, Dinesh; Westwell, Fran; Sturdy, Ann; Barcella, Lara; Soussi, Najwa; Mpelembue, Mushiya; Raj, Sreena; Sharma, Rajni; Corrah, Tumena; Liu, John; Whittington, Ashley; Roche, Siobhan; Wagstaff, Lynda; Farrier, Adam James; Bisnauthsing, Karen; Abeywickrama, Movin; Spence, Niamh; Packham, Alice; Serafimova, Teona; Aslam, Suahil; McGreevy, Caitlin; Borca, Alessandro; DeLosSantosDominguez, Pamela; Palmer, Emily; Broadhead, Samantha; Farooqi, I. Sadaf; Piper, Jo; Weighell, Rowena; Pickup, Lorinda; Shamtally, Djamila; Domingo, Jason; Kourampa, Evgenia; Hale, Colin; Gibney, Jennifer; Stackpoole, Michael; Rashid-Gardner, Zalina; Lyon, Rebecca; McDonnell, Chloe; Cole, Christine L.; Stewart, Anna; McMillan, Gillian; Savage, Mary J.; Beckett, Helen; Moorbey, Chantelle; Desai, Amisha; Brown, C. Wrey; Naker, Kush; Gokani, Karishma; Trinham, Charlotte; Sabine, Charlette; Moore, Sophie E.; Hurdover, Steve; Justice, Edwin; Stone, Megan; Plested, Emma; Silva, Carla Ferreira Da; White, Rachel; Robinson, Hannah; Turnbull, Iain; Morshead, Gertraud; Drake-Brockman, Rachael; Smith, Catherine; Li, Grace; Kasanyinga, Mwila; Clutterbuck, Elizabeth A.; Bibi, Sagida; Singh, Michael J.; Champaneri, Trishna; Irwin, Margaret; Khan, Mohammed; Kownacka, Alicia; Nabunjo, Martha; Osuji, Carol; Hladkiwskyj, John; Galvin, D. A. J.; Patel, Gita; Grierson, Jack; Males, Samantha; Askoolam, Krishna; Barry, Joshua; Mouland, Johanna; Longhurst, Beverley; Moon, Maria; Giddins, Beth; Alves, Carlota Pereira Dias; Richmond, Leah; Minnis, Christine; Baryschpolec, Sonia; Elliott, Scott; Fox, Lauren; Graham, Victoria; Baker, Natalie; Godwin, Kerry; Buttigieg, Karen; Knight, Chanice; Brown, Phillip; Lall, Paminder; Shaik, Imam H.; Chiplin, Emily; Brunt, Emily; Leung, Stephanie; Allen, Lauren; Thomas, S.; Fraser, Sara J.; Choi, Bea; Gouriet, Jade; Perkins, Jonathan A.; Gowland, Andrew; Macdonald, Jonathan; Seenan, John Paul; Starinskij, Igor; Seaton, Andrew; Peters, Erica N.; Singh, Stephen; Gardside, Ben; Bonnaud, Avril; Davies, Ceri H.; Gordón, Elizabeth; Keenan, Samantha; Hall, Jane; Wilkins, Suzanne; Tasker, Suzanne; James, Rob S.; Seath, Ingrid; Littlewood, Kelly; Newman, Joseph P.; Boubriak, Iryna; Suggitt, Debbie; Haydock, Helen; Bennett, Sara; Woodyatt, Wiesia; Hughes, Kerry; Bell, Judith; Coughlan, Tricia; Welsenes, Donald van; Kamal, Mohammed; Cooper, Chris; Tunstall, Simon; Ronan, Nicholas; Cutts, Rebecca; Dare, Tracey; Yim, Yee Ting Nicole; Whittley, Sarah; Hamal, Shama; Ricamara, Marivic; Adams, Kirsty; Baker, Holly; Driver, Kimberley; Turner, Nicola; Rawlins, Todd; Roy, Subarna; Merida-Morillas, Marta; Sakagami, Yukari; Andrews, Antonette; Goncalvescordeiro, Lillian; Stokes, Matthew; Ambihapathy, Wythehi; Spencer, Joanne; Parungao, Nina; Berry, Lisa; Cullinane, James; Presland, Laura; Russell, Amy Ross; Warren, Sarah; Baker, Jonathan; Oliver, Abigail; Buadi, Amanda; Lee, Kyung Hwa; Haskell, Louise; Romani, Rossana; Bentley, Ian; Whitbred, Tim; Fowler, Simon V.; Goldingay, John; Magee, Alan G.; Watson, Tara Marie; Nightingale, Kari; Marius, Phedra; Summerton, Eloise; Locke, Emily; Honey, Thomas; Lingwood, Aidan; Haye, Anastasia de la; Elliott, Ryan Stephen; Underwood, Karen; King, Mikayala; Davies-Dear, Sharon; Horsfall, Emily; Chalwin, Olivia; Burton, Holly; Edwards, Christopher J; Welham, Benjamin; Appleby, Kim; Dineen, Emily; Garrahy, Sarah; Hall, F. G.; Ladikou, Eleni E; Mullan, Dee; Hansen, Daniel; Campbell, Marion K; Santos, Filipa; Lakeman, Nicki; Branney, Debbie; Vamplew, Luke; Hogan, Alison; Frankham, Jorden; Wiselka, Martin; Vail, Denny; Wenn, Victoria; Renals, Valerie; Ellis, Kathryn A.; Lewis-Taylor, Jessica; Habash-Bailey, Haniah; Magán, Javier M.; Hardy, Ann

doi:10.1016/s1473-3099(22)00271-7

Cited by 141 publications

(134 citation statements)

References 11 publications

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“…4 Recently, a fourth dose has been offered in many developed countries to maintain an adequate level of protection against COVID-19. 2 However, the optimal time interval between the booster doses remains under question. The purpose of this study was to examine the kinetics of SARS-CoV-2 neutralizing antibodies (NAbs) after vaccination with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) for a period up to 6 months after the third vaccination (booster dose).…”

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confidence: 99%

“…BNT162b2 administered as first and second booster dose following initial full vaccination leads to significant humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 1,2 In Israel, a third BNT162b2 vaccine shot significantly reduced the risk of SARS-CoV-2 among 1650 triple-vaccinated health care workers compared with 278 double-vaccinated individuals. 3 Importantly, a third dose of the BNT162b2 vaccine improves the protection against severe COVID-19 hospitalizations.…”

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confidence: 99%

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Third Dose of the BNT162b2 Vaccine Results in Sustained High Levels of Neutralizing Antibodies Against SARS-CoV-2 at 6 Months Following Vaccination in Healthy Individuals

Ntanasis‐Stathopoulos

Karalis

Sklirou

et al. 2022

HemaSphere

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confidence: 99%

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confidence: 99%

Third Dose of the BNT162b2 Vaccine Results in Sustained High Levels of Neutralizing Antibodies Against SARS-CoV-2 at 6 Months Following Vaccination in Healthy Individuals

Ntanasis‐Stathopoulos

Karalis

Sklirou

et al. 2022

HemaSphere

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“…Similarly, VE data substantially decreased from 70.1% to 60.9% in mRNA-1273-boosted and 62.4% to 39.6% in BNT162b2-boosted after 10 or more weeks of booster (Andrews et al, 2022). Since there is an evident benefit of a fourth dose seven months after the third dose (Munro et al, 2022), the result showed that the fourth booster elicited a high level of anti-spike IgG in individuals receiving AZD1222/mRNA prime boosters. The additional fourth dose should be optional for those who received the AZD1222 as the third dose due to the lower antibody response in this group.…”

Section: Discussionmentioning

confidence: 99%

Persistence of immunity against omicron BA.1 and BA.2 following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-doses AZD1222 vaccination

Assawakosri

Kanokudom

Chansaenroj³

et al. 2022

Preprint

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ObjectivesThe SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants.MethodsParticipants who completed Oxford/AstraZeneca (hereafter AZD1222) for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and mRNA vaccines (BNT162B2, full or half-dose mRNA-1273) administered six months after primary vaccination were determined.ResultsTotal 229 individuals enrolled, a waning of immunity was observed 5-7 months after the AZD1222-primed. Total RBD immunoglobulin (Ig) levels, anti-RBD IgG and focus reduction neutralization test against Omicron BA.1 and BA.2 and T cell response peaked 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable and well tolerated for all vaccines.ConclusionsA heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared to a homologous booster in individuals with AZD1222-primed vaccinations.

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“…Accordingly, in vitro neutralization assays highlight poor cross-neutralization of Omicron by sera from vaccinees [19, 32-36, 48, 68, 81, 82]. Although booster vaccine dose(s) restore neutralizing antibody (NAb) responses against Delta and partially against Omicron, they do not decrease viral load or transmission [35,36,44,46,48,57,[81][82][83][84][85][86][87][88][89][90].…”

Section: Introductionmentioning

confidence: 99%

Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

Silva

Kohnen

Gilson

et al. 2022

Preprint

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SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here we compared the ability of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and from 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta to neutralize the ancestral B.1 strain, and the Gamma, Delta and Omicron BA.1 variants using live virus. We further determined antibody levels against the Spike protein, the Receptor Binding Domain (RBD) and the N-terminal domain (NTD) of Spike. Convalescent sera featured considerable variability in neutralization of B.1 and in cross-neutralization of different strains, and neutralizing capacity moderately correlated with antibody levels against Spike and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed higher neutralizing ability against all strains than patients with mild or severe forms of disease. Sera from BTI cases fell into one of two categories: half the sera had high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or very low neutralizing activity against all strains. Although antibody levels against Spike and the RBD were lower in BTI cases than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, indicative of cross-neutralization between B.1, Delta and Omicron and suggestive of higher affinity, as confirmed by the IC50:Ab level ratios. Neutralizing activity of BTI sera was strongly correlated with antibodies against Spike and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further suggest that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross neutralizing antibodies against different strains, including Omicron BA.1.

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Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Cited by 141 publications

References 11 publications

Third Dose of the BNT162b2 Vaccine Results in Sustained High Levels of Neutralizing Antibodies Against SARS-CoV-2 at 6 Months Following Vaccination in Healthy Individuals

Third Dose of the BNT162b2 Vaccine Results in Sustained High Levels of Neutralizing Antibodies Against SARS-CoV-2 at 6 Months Following Vaccination in Healthy Individuals

Persistence of immunity against omicron BA.1 and BA.2 following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-doses AZD1222 vaccination

Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

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