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


METHODS
We 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.


RESULTS
The 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.


CONCLUSIONS
These data suggest that pseudovirus neutralization should be used as the preferred humoral immune measure for studying HPV vaccine responses, particularly for non-vaccine genotypes.
Virus Reference Department, Public Health England, London, United Kingdom.
Anna
A
Godi
Virus Reference Department, Public Health England, London, United Kingdom.
Sara L
SL
Bissett
National Vaccine Evaluation Consortium, Public Health England, London, United Kingdom.
Elizabeth
E
Miller
Virus Reference Department, Public Health England, London, United Kingdom.
Simon
S
Beddows
D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002648:Child; D056738:Cross Protection; D005260:Female; D005838:Genotype; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / Q000008:administration & dosage*; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D058952:Human papillomavirus 31 / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007156:Immunologic Memory; D018655:Lymphocyte Count; D009500:Neutralization Tests; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D014611:Vaccination
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18