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
. 2017 Oct 3;13(10):2357-2363.
doi: 10.1080/21645515.2017.1356522. Epub 2017 Aug 24.

Postdose 3 G1 serum neutralizing antibody as correlate of protection for pentavalent rotavirus vaccine

G Frank Liu  1 , Darcy Hille  1 , Susan S Kaplan  1 , Michelle G Goveia  1
Affiliations

Postdose 3 G1 serum neutralizing antibody as correlate of protection for pentavalent rotavirus vaccine

G Frank Liu et al. Hum Vaccin Immunother. .

Abstract

Although clinical trials of the pentavalent rotavirus vaccine (RotaTeq®, RV5) have demonstrated efficacy against RV gastroenteritis (RGE) in low and high-income settings, a clear correlate of protection or a measure of immune response that could predict efficacy has yet to be identified. This is the first time that immunogenicity data with both serum neutralized antibody (SNA) titers and anti-RV IgA titers from several clinical efficacy trials were pooled to provide a unique context for evaluating the correlation between immunogenicity and RGE risk or efficacy of RV5. The correlation between immunogenicity and RGE risk is evaluated with data at the individual subject level. The analyses show that higher Postdose 3 (PD3) G1 SNA titers are associated with lower odds of contracting any RGE. The correlation between immunogenicity and efficacy is assessed using aggregated population level data, which shows higher efficacy associated with higher PD3 G1 SNA geometric mean titer (GMT) ratio (between RV5 and placebo) and PD3 serum anti-RV IgA GMT ratio. Among high-income countries, efficacy plateaus over the range of PD3 G1 SNA GMT ratios and PD3 serum anti-RV IgA GMT ratios. From both individual- and population-level analyses, PD3 G1 SNA titers correlated most closely with the RGE risk or efficacy for RV5.

Keywords: correlation of protection; geometric mean titer (GMT); immunogenicity; pentavalent rotavirus vaccine (RV5); rotavirus gastroenteritis (RGE).

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Scatter plot of efficacy on GMT ratios of SNA for G1 – G4, P1A, and serum anti-rotavirus IgA (aggregated data from P005, P006, P007, P015 and P024). Note: 5L, 5M, 5H = P005 low, middle, and high potency, 5Mo = P005 monovalent, 5Q = P005 quadrivalent, 6F = P006 (Finland), 6U = P006 (US), 7 = P007, 15Af = P015 (Africa), 15A = P015 (Asia), 24 = P024 (China). Dotted lines are smooth spline curves.
Figure 2.
Figure 2.
Weighted regression analyses of efficacy on PD3 G1 SNA GMT ratio (aggregated data from P005, P006, P007, P015 and P024). Note: 5L, 5M, 5H = P005 low, middle, and high potency, 5Mo = P005 monovalent, 5Q = P005 quadrivalent, 6F = P006 (Finland), 6U = P006 (US), 7 = P007, 15Af = P015 (Africa), 15A = P015 (Asia), 24 = P024 (China). Dotted line represents the weighted regression line (p-value = 0.0002).
Figure 3.
Figure 3.
Weighted regression analyses of efficacy on PD3 serum anti-rotavirus IgA GMT ratio (aggregated data from P005, P006, P007, P015 and P024). Note: 5L, 5M, 5H = P005 low, middle, and high potency, 5Mo = P005 monovalent, 5Q = P005 quadrivalent, 6F = P006 (Finland), 6U = P006 (US), 7 = P007, 15Af = P015 (Africa), 15A = P015 (Asia), 24 = P024 (China). Dotted line represents the weighted regression line (p-value = 0.0002).
Figure 4.
Figure 4.
Weighted regression analyses of efficacy on PD3 G1 SNA GMT ratio (aggregated data from final formulation in P005, P006, and P007). Note: 5L = P005 low potency, 5M = P005 middle potency, 5H = P005 high potency, 6F = P006 (Finland), 6U = P006 (US), 7 = P007. Dotted line represents the weighted regression line (p-value = 0.3958).
Figure 5.
Figure 5.
Weighted regression analyses of efficacy on PD3 anti-rotavirus IgA GMT ratio (aggregated data from final formulation in P005, P006, and P007). Note: 5L = P005 low potency, 5m = P005 middle potency, 5H = P005 high potency, 6F = P006 (Finland), 6U = P006 (US), 7 = P007. Dotted line represents the weighted logit regression line (p-value = 0.0890).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD, World Health Organization–Coordinated Global Rotavirus Surveillance Network . Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000–2013. Clin Infect Dis. 2016;62(Suppl 2):S96-S105. doi:10.1093/cid/civ1013. PMID:27059362 - DOI - PMC - PubMed
    1. Staat MA, Azimi PH, Berke T, Roberts N, Bernstein DI, Ward RL, Pickering LK, Matson DO. Clinical presentations of rotavirus infection among hospitalized children. Pediatr Infect Dis J. 2002;21:221-7. doi:10.1097/00006454-200203000-00012. PMID:12005086 - DOI - PubMed
    1. Parashar UD, Burton A, Lanata C, Boschi-Pinto C, Shibuya K, Steele D, Birmingham M, Glass RI. Global mortality associated with rotavirus disease among children in 2004. J Infect Dis. 2009;200(Suppl 1):S9-S15. doi:10.1086/605025. PMID:19817620 - DOI - PubMed
    1. Tate JE, Patel MM, Steele AD, Gentsch JR, Payne DC, Cortese MM, Nakagomi O, Cunliffe NA, Jiang B, Neuzil KM, et al.. Global impact of rotavirus vaccines. Expert Rev Vaccines. 2010;9(4):395-407. doi:10.1586/erv.10.17. PMID:20370550 - DOI - PubMed
    1. Kapikian AZ, et al. Rotavirus. In: Kripe DM, editor(s). Fields virology. Vol 2 4th ed Lippincott Williams & Wilkins; 2001. p. 1787-825.

Publication types

MeSH terms