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AuthorJagu, Subhashini
AuthorKaranam, Balusubramanyam
AuthorWang, Joshua W.
AuthorZayed, Hatem
AuthorWeghofer, Margit
AuthorBrendle, Sarah A.
AuthorBalogh, Karla K.
AuthorTossi, Kerstin Pino
AuthorRoden, Richard B.S.
AuthorChristensen, Neil D.
Available date2016-11-06T08:36:49Z
Publication Date2015-10-13
Publication NameVaccineen_US
CitationSubhashini Jagu, Balusubramanyam Karanam, Joshua W. Wang, Hatem Zayed, Margit Weghofer, Sarah A. Brendle, Karla K. Balogh, Kerstin Pino Tossi, Richard B.S. Roden, Neil D. Christensen, Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes, Vaccine, Volume 33, Issue 42, 13 October 2015, Pages 5553-5563
AbstractVaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum±MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant.
SponsorMedigene AG to NDC and RBSR, and Public Health Service ( grants P50 CA098252 and CA118790 to RBSR.
PublisherElsevier, Ltd
SubjectHuman papillomavirus
SubjectNeutralizing antibody
SubjectAdeno-associated virus
TitleDurable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes
Issue Number42
Volume Number33

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