Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2023 May 5:rs.3.rs-2653179.
doi: 10.21203/rs.3.rs-2653179/v1.

Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial

Angela Branche  1 , Nadine Rouphael  2 , David Diemert  3 , Ann Falsey  1 , Cecilia Losada  4 , Lindsey R Baden  5 , Sharon Frey  6 , Jennifer Whitaker  7 , Susan Little  8 , Evan Anderson, Emmanuel Walter  9 , Richard Novak  10 , Richard Rupp  11 , Lisa Jackson  12 , Tara Babu  13 , Angelica Kottkamp  14 , Annie Luetkemeyer  15 , Lilly Immergluck  16 , Rachel Presti  17 , Martin Backer  18 , Patricia Winokur  19 , Siham Mahgoub  20 , Paul Goepfert  21 , Dahlene Fusco, Elissa Malkin  3 , Jeff Bethony  3 , Edward Walsh  1 , Daniel Graciaa  22 , Hady Samaha  23 , Amy Sherman  24 , Stephen Walsh  25 , Getahun Abate  6 , Zacharoula Oikonomopoulou  6 , Hana El Sahly  7 , Thomas Martin  26 , Satoshi Kamidani  27 , Michael Smith  28 , Benjamin Ladner  10 , Laura Porterfield  11 , Maya Dunstan  29 , Anna Wald  13 , Tamia Davis  14 , Robert Atmar  7 , Mark Mulligan  30 , Kirsten Lyke  31 , Christine Posavad  32 , Megan Meagher  33 , David Stephens  34 , Kathleen Neuzil  35 , Kuleni Abebe  36 , Heather Hill  37 , Jim Albert  38 , Kalyani Telu  37 , Jinjian Mu  37 , Teri Lewis  39 , Lisa Giebeig  39 , Amanda Eaton  40 , Antonia Netzl  41 , Sam Wilks  42 , Sina Tureli  41 , Mamodikoe Makhene  43 , Sonja Crandon  44 , David Montefiori  45 , Mat Makowski  37 , Derek Smith  41 , Seema Nayak  44 , Paul Roberts  43 , John Beigel  46
Affiliations

Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial

Angela Branche et al. Res Sq. .

Update in

  • Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.
    Branche AR, Rouphael NG, Diemert DJ, Falsey AR, Losada C, Baden LR, Frey SE, Whitaker JA, Little SJ, Anderson EJ, Walter EB, Novak RM, Rupp R, Jackson LA, Babu TM, Kottkamp AC, Luetkemeyer AF, Immergluck LC, Presti RM, Bäcker M, Winokur PL, Mahgoub SM, Goepfert PA, Fusco DN, Malkin E, Bethony JM, Walsh EE, Graciaa DS, Samaha H, Sherman AC, Walsh SR, Abate G, Oikonomopoulou Z, El Sahly HM, Martin TCS, Kamidani S, Smith MJ, Ladner BG, Porterfield L, Dunstan M, Wald A, Davis T, Atmar RL, Mulligan MJ, Lyke KE, Posavad CM, Meagher MA, Stephens DS, Neuzil KM, Abebe K, Hill H, Albert J, Telu K, Mu J, Lewis TC, Giebeig LA, Eaton A, Netzl A, Wilks SH, Türeli S, Makhene M, Crandon S, Montefiori DC, Makowski M, Smith DJ, Nayak SU, Roberts PC, Beigel JH; COVAIL Study Group. Branche AR, et al. Nat Med. 2023 Sep;29(9):2334-2346. doi: 10.1038/s41591-023-02503-4. Epub 2023 Aug 28. Nat Med. 2023. PMID: 37640860 Free PMC article. Clinical Trial.

Abstract

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Pseudovirus Neutralization ID50 Titers by Timepoint (Baseline, Day 29 and Day 91) and Variant (D614G, Delta, Beta, Omicron BA.1 [B.1.1.529] and Omicron BA.4/BA.5) in Uninfected Participants by vaccine arm and platform.
Circles denote GMT, geometric mean titer with 95% CI. GMT at pre-vaccination baseline, obtained on Day 1 are presented in blue and post-vaccination Day 29 GMT and Day 91 GMT in red and yellow, respectively.
Figure 2
Figure 2. Pseudovirus Neutralization ID50 Titers by Timepoint (Day 1, Day 15 and Day 91) and Variant (D614G, Omicron BA.1, BA.2.12.1, BA.4/BA.5, BA.2.75, BA.4.6, BF.7, BA.2.75.2, BQ.1.1 and XBB.1) in a Subset (N = 22-23) of Uninfected Participants:
A) Stage 1 Moderna mRNA-1273 Prototype monovalent vaccine. Boxes and horizontal bars denote interquartile range (IQR) and median ID50, respectively. Whisker denotes 95% confidence interval. LLOD, lower limit of detection of the assay. GMT, geometric mean titer. GMRD614G, geometric mean ratio against D614G. N, number of samples tested. B) Stage 1 Moderna mRNA-1273 Omicron BA.1 + Prototype bivalent vaccine. Boxes and horizontal bars denote interquartile range (IQR) and median ID50, respectively. Whisker denotes 95% confidence interval. LLOD, lower limit of detection of the assay. GMT, geometric mean titer. GMRD614G, geometric mean ratio against D614G. N, number of samples tested. C) Radar plots of the pseudovirus neutralization GMTs at Day 15 for the two vaccine arms in Stage 1 Moderna mRNA-1273 Prototype monovalent vaccine (red) and Moderna mRNA-1273 Omicron BA.1 + Prototype bivalent vaccine (blue). Circles are GMT estimates for each variant. D) Radar plots of the pseudovirus neutralization GMTs at Day 91 for the two vaccine arms in Stage 1 Moderna mRNA-1273 Prototype monovalent vaccine (red) and Moderna mRNA-1273 Omicron BA.1 + Prototype bivalent vaccine (blue). In the radar plots, each variant is represented by its own vertical line or spoke, and the spokes are evenly distributed around the circle. Each horizontal line along a vertical spoke represents the Geometric Mean Titer (GMT) at a 10-fold dilution with the value closest to the center being 1 and farthest from the center being 10,000 or 104. A line is drawn connecting the GMT data values for vaccine arm at the individual variants represented by its vertical spoke.
Figure 3
Figure 3. Antigenic Cartography.
A) An adapted version of the antigenic map by Wilks, et al. served as base map for all antibody landscapes. Virus variants are shown as filled circles, variants with additional substitutions from their root variant as smaller circles. Individual sera are displayed as open squares in the color of their root variant or grey for mRNA-1273 vaccinated sera, small dark squares represent clinical trial participants. One grid unit in the map corresponds to a two-fold dilution in the neutralization assay, within x- and y-axis the map orientation is free as antigenic distances are relative. Small triangles point to sera outside the shown map area. B) Day 1 and Day 91 geometric mean titer (GMT) antibody landscapes for uninfected and infected individuals in different arms for the 3 stages. Impulses show the GMT against the specific variant. Lower landscapes correspond to Day 1 and upper landscapes to Day 91 immunity. To interpret landscapes, a Day 91 response where upper landscape is flat, indicates the responses to all the variants were equivalent, whereas, skewing up or down indicates an uneven response across variants. The surface colors represent study arms (Red: Prototype, Light Green: Prototype + Omicron BA.1, Black: Omicron BA.1, Dark Green: Delta + Omicron BA.1, Blue: Beta + Omicron BA.1, Purple: Beta + Prototype, Yellow: Beta).
See this image and copyright information in PMC

References

    1. WHO. World Health Organization, Weekly Operational Update on COVID-19. https://wwwwhoint/emergencies/diseases/novel-coronavirus-2019/situation-... 2020a;Accessed January 20, 2022..
    1. JHU. COVID-19 Dashboard, Center for Systems Science and Engineering (CCSE) at Johns Hopkins University (JHU). https://coronavirus.jhu.edu/map.html.;Accessed January 20, 2022.
    1. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403–416. - PMC - PubMed
    1. Bos R, Rutten L, van der Lubbe JEM, et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines. 2020;5:91. - PMC - PubMed
    1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020;383(27):2603–2615. - PMC - PubMed

Publication types

Associated data