Biomedical subjects

Alan R Shaw

Publications and source records attributed to Alan R Shaw.

6 recordsLinked to original sources

PubMed2006

The rotavirus vaccine saga.

Rotavirus is the single most common cause of acute, dehydrating gastroenteritis worldwide. This is a highly contagious and highly democratic disease. The attack rate in infants and young children is similar regardless of sanitation, socioeconomics or geography. Rotavirus vaccine development began in the early 1980s using a "Jennerian" approach based on rotaviruses that normally infect animals. Although these vaccines were found to be generally safe, protection from disease was inconsistent. The second generation of vaccines was based on the same animal viruses configured to carry the relevant coat proteins of human rotaviruses. An attenuated human rotavirus vaccine has also been developed. After close to 20 years of laboratory and clinical studies, safe and effective rotavirus vaccines are approaching regulatory approval.

Child↗

PubMed2005

Human papillomavirus vaccines in development: if they're successful in clinical trials, how will they be implemented?

INTRODUCTION: There are some 30-40 genotypes of human papillomavirus (HPV) that cause anogenital lesions in humans, primarily cervical, vaginal, and vulvar dysplasias and cancer in women, anal dysplasias in some men, and genital warts in both sexes. METHODS: Both GlaxoSmithKline and Merck companies are developing vaccines for the prevention of HPV infection. RESULTS: Both vaccines stimulate an antibody response against HPV types 16 and 18; the Merck vaccine also include HPV types 6 and 11. CONCLUSIONS: This report focuses on progress with both prophylactic vaccines and introduces strategies for global immunization.

Clinical Trials as Topic↗

PubMed2005

Novel rotavirus VP7 typing assay using a one-step reverse transcriptase PCR protocol and product sequencing and utility of the assay for epidemiological studies and strain characterization, including serotype subgroup analysis.

Rotavirus is the most common cause of severe dehydrating gastroenteritis in infants. To date, 10 different serotypes of rotavirus have been identified in human stools. While four or five serotypes dominate, serotype circulation varies with season and geography. Since our laboratory has been involved in the development of a multivalent rotavirus vaccine, it is important to identify the serotypes of rotavirus encountered during our clinical trials. We have developed methodologies for the molecular identification of rotavirus strains based on VP7 gene segment sequence. A 365-bp reverse transcriptase PCR product was generated from the VP7 gene segment using a pair of novel degenerate primers. All serotypes tested (both animal and human) yielded an identically sized product after amplification. Sequencing of these products is performed using truncated versions of the original primers. The sequence generated is compared against a database of rotavirus VP7 sequences, with the G type determined, based on the sequence homology. Using this assay, we have correctly identified human VP7 strains from a panel of available serotypes, as well as numerous animal strains. The assay was qualified using rotavirus positive stool samples, negative stool samples, and rotavirus-spiked stool samples. In addition, samples from cases of acute gastroenteritis collected at Children's Hospital of Philadelphia have been evaluated and indicate that the assay is able to discriminate subtle differences within serotypes. The assay has been utilized in the testing of >3,000 antigen-positive (enzyme immunoassay) samples collected during clinical trials of a rotavirus vaccine (RotaTeq) and identified a serotype in approximately 92% of samples (3, 17, 19).

Amino Acid Sequence↗

PubMed2004

Infant immune response to human rotavirus serotype G1 vaccine candidate reassortant WI79-9: different dose response patterns to virus surface proteins VP7 and VP4.

BACKGROUND: Rotavirus is the leading cause of morbidity from gastroenteritis in the developed world and the leading cause of mortality from viral gastroenteritis (estimated 600000 deaths) worldwide. G1 is the most prevalent human serotype. Reassortant rotavirus between simian rotavirus RRV or bovine rotavirus WC3 and human strain rotaviruses have been extensively tested as candidate vaccines. Rotavirus (RV) reassortant strain WI79-9 consists of a human (strain WI79) G1 serotype VP7 surface protein on a bovine (strain WC3) background. It is a key component of a pentavalent (G1, G2, G3, G4 and P1) WC3 reassortant vaccine candidate, RotaTeq, now being tested in Phase III clinical trials. METHODS: We studied 84 infants between the ages of 2 and 8 months who received 3 oral doses of WI79-9. Serum neutralizing antibody was measured to the human (WI79 serotype P1 G1) and bovine (WC3 serotype P7 G6) parent RV after each dose. A significant response was defined as a > or =3-fold rise in antibody titer between the predose and postdose sera. RESULTS: In two separate cohorts of vaccinees given three doses of WI79-9 reassortant rotavirus, 68 to 75% of infants demonstrated a significant response to WC3 (VP4, P7) after Dose 1, fewer (24 to 39%) responses were detected after Dose 2 and rare (0 to 4%) additional responses occurred after Dose 3. The cumulative response rate to WC3 after three doses was 95% in both trials. In contrast 23 to 37% had a significant response to WI79 (VP7, G1) after Dose 1, and 57 to 61% had a significant response after Dose 2. Additional significant responses after Dose 3 led to a cumulative response of 70 to 84%. CONCLUSION: Two doses of G1 reassortant WI79 were necessary to induce significant antibody responses to human G1 (VP7) antigen in >50% of infants. Three doses were required to achieve significant antibody responses to VP7 in >70% of infants.

Animals↗

PubMed2004

Human papillomavirus vaccines and prevention of cervical cancer.

Cervical cancer and precancerous cervical lesions constitute a major problem in women's health. Every year 470,000 cases of cervical cancer are diagnosed worldwide, and about half the women afflicted will die. In the United States alone, approximately 14,000 cases of cervical cancer are diagnosed each year despite the availability of screening and access to high-quality gynecological care. With the confirmation that cervical cancer is caused by an infectious agent, human papillomavirus, the possibility of fighting this disease with either prophylactic or therapeutic vaccination arose. This review describes advances in vaccine development and very promising first results for prophylactic vaccination against cervical cancer.

Cancer Vaccines↗

PubMed2003

Rapid method for the characterization of 3' and 5' UTRs of influenza viruses.

A T4 RNA ligase based strategy is demonstrated that allows for the full characterization of 3' and 5' UTR regions of negative strand RNA viruses. Negative strand RNA viruses such as influenza have 3'OH and 5'P terminal ends that are capable of being ligated using T4 RNA ligase. Each segment can form a mixture of linear concatamers between like and different viral segments or can itself form a circular structure upon ligation. RT-PCR can then be performed on these circular RNA segments using gene specific primers subsequently allowing for the characterization of the true terminal sequence for each viral segment. The UTR regions of a number of influenza virus strains were defined accurately using this approach.

3' Untranslated Regions↗