Vaccine Guru

In a fantastic new paper by Chung et al., (2014) that accompanied the paper described in my previous Blog by Yates et al., (2014), the role played by IgG3 has been described very elegantly in the context of 2 HIV vaccines-RV144 and VAX003. Chung et al., show how IgG3 might be able to fight HIV infection in the absence of viral neutralization. Background: RV144: ALVAC-HIVvCP1521 prime and recombinant gp120 AIDSVAX B/E boose                      VAX003: AIDSVAX B/E bivalent rgp120 given with alum in 7 doses Results: * RV144 elicited a polyfunctional antibody response associated with the selective induction of IgG3 antibodies. * VAX003 elicited a monofunctional antibody response characterized by selection of the functionally inert IgG4 antibody subclass, likely due to repeated administration of gp120 protein vaccination which decreased IgG3 subclass levels. *RV144 induced both IgG1 and IgG3 antibodies targeting the V2 crown,...

There have been a series of papers describing the " Antibody Profile " of participants in the partially successful RV144 Trial that I had described earlier. The first paper looking at the antibody type is a paper by Nicole Yates that appeared in Science Trans Med (2014) . Very little is known about the protective role of vaccine-induced IgG3 antibodies for HIV-1. Previously, it was found that a best known anti-HIV-1 antibody, 2F5, is of IgG3 origin. In the paper by Yates et al., they compared antibody profiles of RV144 trial and the VAX003 trial, which was a modification of the RV144 vaccine. Background: RV144 consists of (cladeB/E) ALVAC prime plus 2 protein boosts rgp120 boost VAX003: consists of (cladeB/E) gp120 protein immunogen. Results: *It was found that IgG3 response rates were significantly higher in RV144 compared to VAX003 at peak immunogenicity time point. **V1-V2 IgG3 antibodies correlated with decreased risk of infection in RV144. ...

 From T cells to Antibodies: Back and Forth search for an ideal HIV vaccine With negative data pouring out of major Clinical Trials associated with  HIV-1 vaccines, even though some are encouraging, emphasis has shifted from T cell-based vaccines to Antibody-based vaccines. This is mainly due to precise determination of HIV-1 protein structure, that has been corroborated by several laboratories. Additionally, the isolation of broadly neutralizing antibodies from patients who resist the disease (CAPRISA), further invigorated the vaccine community. What does this mean for vector development? Louis Picker's groundbreaking study in Rhesus macaques showing significant protection against SIV challenge using a cytomegalovirus vector determined that the mechanism is due to an unconventional induction of CD8 T cell response restricted by MHC class II proteins. Is this system unique to SIV? Will this work in HIV? While it is too early to tell, the next best experiment would be to ...

  A Phase III Trial of Sanofi Pasteur Live Recombinant ALVAC-HIV (vCP1521) Priming With VaxGen gp120 B/E (AIDSVAX B/E) Boosting in HIV-Uninfected Thai Adults. Background: RV114 was a Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study carried out in Thailand. This prime-boost test-of-concept trial began in 2003 and enrolled 15403 HIV-negative Thai men and women between the ages of 18 and 30. The vaccine consisted of 2 regimens: ALVAC (prime) and AIDSVAX B/E (boost). The vaccine consisted of synthetic fragments of genetic components of HIV- subtypes B and E (CRF01 AE).  End points: Whether vaccine reduced risk of HIV infection and whether vaccinated individuals who acquired HIV had lower viral loads than placebo group. To determine statistical significance, data were analyzed according to 1. Intent to treat (ITT) 2. Modified Intent to treat (mITT) and 3. Per Protocol (PP). R...

HVTN/STEP Trial: A vaccine that surprised many with increased risk of disease in vaccinees: A Phase IIb ‘test of concept’ trial of Merck’s MRKAd5 HIV-1 gag/pol/nef trivalent vaccine based on a weakened non-replicating adenovirus (type 5 adenovirus). This was a Randomized, double blind, placebo control study carried out in North America, South America, Caribbean and Australia This trial enrolled 3000 adult HIV negative high-risk population from a diverse background (gay/MSM, female sex workers 18-45 years of age). The study had 62% males and 38% females. First enrolment was in Dec 2004 and the enrolment was completed in March 2007. The primary efficacy endpoints: Whether the vaccine prevented HIV infection and whether the vaccine reduced the viral load in those who were infected. Results: The vaccine did not prevent infection: in the 741 volunteers who received at least one dose of the three-dose vaccine series, 24 cases of HIV infection were observed and 21 cases of HIV ...

Vaccines have saved more lives than any other drugs. It is true that Big Pharma continues to profit from vaccines but developing vaccines is a high-stakes affair with billions invested. There are obvious ROI issues that prompt pharmaceutical companies to develop drugs against diseases. In an era of massive globalization, where information is only a swipe away, there needs to be continuous oversight of scientific data supporting vaccines.  Browsing through Facebook, one is inundated by posts linking vaccines to development of various diseases, most infamous among them being autism. Similarly, there are various other autoimmune and inflammatory diseases associated with vaccines. The accompanying posts and comments are often vitriolic, with arguments for and against vaccines. While I do not wish to enter the debates favoring either camp, this Blog aims to dissect the science behind vaccines and to flesh out the scientific aspects of vaccine development. ...