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In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.

Publication ,  Journal Article
Kazimbaya, KM; Chisenga, CC; Simuyandi, M; Phiri, CM; Laban, NM; Bosomprah, S; Permar, SR; Munsaka, S; Chilengi, R
Published in: PLoS One
2020

BACKGROUND: Despite contributing to a significant reduction in rotavirus associated diarrhoea in highly burdened low- and middle-income countries, live attenuated, oral rotavirus vaccines have lower immunogenicity and efficacy in these settings in comparison to more developed countries. Breastmilk has been implicated among factors contributing to this lowered oral vaccine efficacy. We conducted in-vitro experiments to investigate the inhibitory effects of maternal antibody and other non-antibody components in breastmilk on rotavirus vaccine strain (Rotarix) multiplication in MA104 cell culture system and assessed associations with in-vivo vaccine seroconversion in vaccinated infants. METHODS: Breastmilk samples were collected from mothers before routine rotavirus vaccination of their infant at 6 weeks of age. For each sample, whole breastmilk, purified IgA, purified IgG and IgG and IgA depleted breastmilk samples were prepared as exposure preparations. A 96 well microtitre plate was set up for each sample including a control in which only MA104 cells were grown as well as a virus control with MA104 cells and virus only. The outcome of interest was 50% inhibition dilution of each of the exposure preparations calculated as the titer at which 50% of virus dilution was achieved. Samples from 30 women were tested and correlated to vaccine seroconversion status of the infant. HIV status was also correlated to antiviral breastmilk proteins. RESULTS: The mean 50% inhibitory dilution titer when whole breastmilk was added to virus infected MA104 cells was 14.3 (95% CI: 7.1, 22.7). Incubation with purified IgG resulted in a mean 50% inhibitory dilution of 5 (95%CI -1.6, 11.6). Incubating with purified IgA resulted in a mean 50% inhibitory dilution of 6.5 (95% CI -0.7, 13.7) and IgG and IgA depleted breastmilk did not yield any inhibition with a titer of 1.06 (95%CI 0.9, 1.2). Higher milk IgA levels contributed to a failure of infants to seroconvert. HIV was also not associated with any antiviral breastmilk proteins. DISCUSSION AND CONCLUSION: Whole breastmilk and breastmilk purified IgG and IgA fractions showed inhibitory activity against the rotavirus vaccine Rotarix™ whilst IgA and IgG depleted breastmilk with non-antibody breastmilk fraction failed to show any inhibition activity in-vitro. These findings suggest that IgA and IgG may have functional inhibitory properties and indicates a possible mechanism of how mothers in rotavirus endemic areas with high titres of IgA and IgG may inhibit viral multiplication in the infant gut and would potentially contribute to the failure of their infants to serocovert. There was not association of HIV with either lactoferrin, lactadherin or tenascin-C concentrations.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2020

Volume

15

Issue

11

Start / End Page

e0240714

Location

United States

Related Subject Headings

  • Virus Replication
  • Vaccines, Attenuated
  • Seroconversion
  • Rotavirus Vaccines
  • Rotavirus
  • Milk, Human
  • Infant
  • In Vitro Techniques
  • Immunoglobulin G
  • Immunoglobulin A
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kazimbaya, K. M., Chisenga, C. C., Simuyandi, M., Phiri, C. M., Laban, N. M., Bosomprah, S., … Chilengi, R. (2020). In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine. PLoS One, 15(11), e0240714. https://doi.org/10.1371/journal.pone.0240714
Kazimbaya, Katayi Mwila, Caroline C. Chisenga, Michelo Simuyandi, Cynthia Mubanga Phiri, Natasha Makabilo Laban, Samuel Bosomprah, Sallie R. Permar, Sody Munsaka, and Roma Chilengi. “In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.PLoS One 15, no. 11 (2020): e0240714. https://doi.org/10.1371/journal.pone.0240714.
Kazimbaya KM, Chisenga CC, Simuyandi M, Phiri CM, Laban NM, Bosomprah S, et al. In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine. PLoS One. 2020;15(11):e0240714.
Kazimbaya, Katayi Mwila, et al. “In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.PLoS One, vol. 15, no. 11, 2020, p. e0240714. Pubmed, doi:10.1371/journal.pone.0240714.
Kazimbaya KM, Chisenga CC, Simuyandi M, Phiri CM, Laban NM, Bosomprah S, Permar SR, Munsaka S, Chilengi R. In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine. PLoS One. 2020;15(11):e0240714.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2020

Volume

15

Issue

11

Start / End Page

e0240714

Location

United States

Related Subject Headings

  • Virus Replication
  • Vaccines, Attenuated
  • Seroconversion
  • Rotavirus Vaccines
  • Rotavirus
  • Milk, Human
  • Infant
  • In Vitro Techniques
  • Immunoglobulin G
  • Immunoglobulin A