Relationship between Humoral Immune Responses against HPV16, HPV18, HPV31 and HPV45 in 12-15 Year Old Girls Receiving Cervarix® or Gardasil® Vaccine

Abstract

BackgroundHuman papillomavirus (HPV) vaccines confer protection against the oncogenic genotypes HPV16 and HPV18 through the generation of type-specific neutralizing antibodies raised against virus-like particles (VLP) representing these genotypes. The vaccines also confer a degree of cross-protection against HPV31 and HPV45, which are genetically-related to the vaccine types HPV16 and HPV18, respectively, although the mechanism is less certain. There are a number of humoral immune measures that have been examined in relation to the HPV vaccines, including VLP binding, pseudovirus neutralization and the enumeration of memory B cells. While the specificity of responses generated against the vaccine genotypes are fairly well studied, the relationship between these measures in relation to non-vaccine genotypes is less certain.MethodsWe carried out a comparative study of these immune measures against vaccine and non-vaccine genotypes using samples collected from 12–15 year old girls following immunization with three doses of either Cervarix® or Gardasil® HPV vaccine.ResultsThe relationship between neutralizing and binding antibody titers and HPV-specific memory B cell levels for the vaccine genotypes, HPV16 and HPV18, were very good. The proportion of responders approached 100% for both vaccines while the magnitude of these responses induced by Cervarix® were generally higher than those following Gardasil® immunization. A similar pattern was found for the non-vaccine genotype HPV31, albeit at a lower magnitude compared to its genetically-related vaccine genotype, HPV16. However, both the enumeration of memory B cells and VLP binding responses against HPV45 were poorly related to its neutralizing antibody responses. Purified IgG derived from memory B cells demonstrated specificities similar to those found in the serum, including the capacity to neutralize HPV pseudoviruses.ConclusionsThese data suggest that pseudovirus neutralization should be used as the preferred humoral immune measure for studying HPV vaccine responses, particularly for non-vaccine genotypes.

Recurrent respiratory papillomatosis (RRP)–time for a reckoning?

“…The quadrivalent HPV L1 vaccine has been proven to provide excellent prophylaxis against infection with the 4 HPV types at the primary sites of the cervix and anus, and also some cross‐protection against non‐vaccine types (closely‐related types) 11, 12…”

“…The quadrivalent HPV L1 vaccine has been proven to provide excellent prophylaxis against infection with the 4 HPV types at the primary sites of the cervix and anus, and also some cross-protection against non-vaccine types (closely-related types). 11,12 The high production of anti-L1 antibodies induced by the quadrivalent vaccine has been shown to be the primary mechanism of prophylaxis against infection by the 4 main HPV types. It is unclear whether this high protective antibody level is able to yield therapeutic benefits in patients already infected with the virus and with the disease.…”

Virus-Like Particles as an Instrument of Vaccine Production

“…Second, VLPs stimulate B-lymphocytes and induce T-lymphocytes in the same manner as does the virus infecting the host organism [30]. For example, VLPs formed by the main capsid protein L1 of the human papilloma virus of several serotypes are successfully used as vaccines against cervical cancer [37]. A vaccine against hepatitis B virus has been produced which contains VLPs in the lipid membrane envelope [38].…”

“…The most wellknown are the Cervarix® and Gardasil® vaccines against cervical cancer, which have been successfully used for prophylaxis of this disease in girls for more than ten years. Both vaccines are based on VLPs formed by the main capsid protein L1 of the human papilloma virus belonging to several serotypes [37]. Engerix and Recombivax HB vaccines against the hepatitis B virus representing VLPs enveloped in a lipid membrane [38], as well as Hecolin and Xiamen Innovax vaccines against hepatitis E [88], were developed and commercialized.…”

Seleção de motivos semelhantes a Papilomavírus, a partir de bibliotecas de phage display, que apresentem potencial aplicação translacional

“…Because over 80% of all HPV associated cancers occur in the cervix, nearly all of the evidence for prophylactic vaccine prevention of incident type-specific HPV infection is in cervical disease (TORRE et al, 2015 Immunogenicity, indicated by antibody titre levels is the primary recognized endpoint in VLP based HPV vaccine studies and titres are dependent on the number of doses and timing (LEHTINEN et al 2012). Studies showed that seropositivity for anti-HPV16 titers after 5 years is high for both Cervarix and Gardasil (GODI et al, 2015) and Gardasil9 induces similar anti-HPV16/18 responses as Gardasil (GUEVARA et al, 2017).…”